The DOI matches its Crossref record; 176 of the 176 references it cites were found in a registry or an index; 7 of the 192 sources its claims cite were checked for support.
Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance
Open accessAbstract
Immune checkpoint inhibitors (ICIs) have made an indelible mark in the field of cancer immunotherapy. Starting with the approval of anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advanced-stage melanoma in 2011, ICIs—which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)—quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival. However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses, and immune-related adverse events complicate treatment. Thus, a better understanding of the requirements for an effective and safe antitumor immune response following ICI therapy is needed. Studies of both tumoral and systemic changes in the immune system following ICI therapy have yielded insight into the basis for both efficacy and resistance. Ultimately, by building on these insights, researchers should be able to combine ICIs with other agents, or design new immunotherapies, to achieve broader and more durable efficacy as well as greater safety. Here, we review the history and clinical utility of ICIs, the mechanisms of resistance to therapy, and local and systemic immune cell changes associated with outcome.
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Claims the paper makes
98 Not checked yet · 27 Own interpretation · 12 No basis given · 2 Partly supported · 1 Own result · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Examination of the lymphocytes that correlated with such beneficial outcomes has repeatedly implicated effector and memory CD8 + T cell and NK cell populations (136-141).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [136] source
- Partly supportedcites [137] sourceExperimental — accuracy not yet measured
The Results report that CD8+ effector-memory cells were significantly more frequent in anti-CTLA-4 responders, while the Discussion links activated NK-cell subsets to better anti-PD-1 response. The paper does not support the broader implication that terminal-effector CD8+ cells or NK cells generally correlate with benefit: terminal-effector CD8+ cells tended to be lower in responders without statistical significance, and overall NK-cell frequencies did not differ significantly. (LLM, conf=0.84)
- Partly supportedcites [138] sourceExperimental — accuracy not yet measured
The section “Clinical response is associated to the generation of memory T cells” reports a sustained increase in effector and terminal effector memory CD8+ T cells among patients with disease control after ipilimumab. The passages from our copy do not establish a corresponding link between NK cells and beneficial outcomes, so the NK-cell part is unsupported. (LLM, conf=0.87)
- Partly supportedcites [139] sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports higher NK-cell frequency in responders, supporting the NK-cell portion. The Results (page unavailable) found no significant association between CD8+ effector-memory or other CD8+ subsets and clinical response, so this paper does not support that portion of the claim. (LLM, conf=0.90)
- Partly supportedcites [140] sourceExperimental — accuracy not yet measured
The Results section on tumor-infiltrating CD45RO+CD8+ T cells links CD8+ effector-memory cells to response to PD-1 blockade. But the Discussion says the authors could not document an increase in CD8+ cells with an effector phenotype, and the Results section on intratumoral leukocytes reports no significant change in NK cells on treatment. This source therefore supports the memory CD8+ portion, not the full list of populations implicated in beneficial outcomes. (LLM, conf=0.90)
- Not checked yetcites [141] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
In the paper
“In a phase I clinical trial of patients with advanced-stage, ipilimumab-refractory melanoma, 26% of participants treated with pembrolizumab, an anti-PD-1 antibody, demonstrated either a complete or partial response (57).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [57] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Perhaps the most prominent predictive markers of effective ICI therapy are the compositions of immune cells within tumors and in the periphery in patients prior to and after therapy.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“Atezolizumab was initially approved by the FDA for the treatment of localized and metastatic urothelial carcinoma on the basis of results of a phase II clinical trial that showed overall response rates of 10% in patients whose disease had progressed after platinumbased chemotherapy treatment (65).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [65] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In fact, peripheral immune responses are critical in achieving favorable clinical outcomes.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ICIs work not only by invigorating T cells but also by activating other cells of the innate and adaptive arms, all of which function in concert to orchestrate an effective response against tumors.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Despite the fact that many patients experience dramatic tumor regression in response to ICIs, most patients and cancers do not respond to these therapies.”
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
“only a minority of patients treated with ICIs achieve a durable response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
None of the sources cited for this claim have been checked yet.
In the paper
“However, despite the success of ICIs, resistance to these agents restricts the number of patients able to achieve durable responses”
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
“only a minority of patients treated with ICIs achieve a durable response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Similar to CTLA-4, engagement of PD-1 with its ligands, PD-L1 and PD-L2, leads to suppression of T cell immune responses (36,37).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ICI-driven changes in the immune response are observed both within tumors and in peripheral organs, such as the draining lymph nodes and peripheral blood.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
In the paper
“The potency of anti-PD-1 in the clinic was further proved by its recent, first-in-class FDA approval as a tissueagnostic therapy for any unresectable or metastatic tumors exhibiting microsatellite instability or deficient mismatch repair (62).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [62] source
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“to date, atezolizumab, in combination with chemotherapy, has been approved by the FDA for the treatment of squamous and nonsquamous NSCLC, small cell lung cancer, and PD-L1-positive triple-negative breast cancer (66)(67)(68)(69).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Both PD-L1 and PD-L2 are expressed on hematopoietic and nonhematopoietic cells, including APCs and cancer cells (36,37).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although we do not yet fully understand the mechanisms responsible for either form of resistance”
- Also stated in: § Acquired Resistance · plain
“Unlike primary resistance to ICIs, acquired resistance, also known as secondary resistance, is not as well understood.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Acquired Resistance · plain
None of the sources cited for this claim have been checked yet.
In the paper
“CTLA-4 inhibits T cell activity through both T cell-intrinsic and T cell-extrinsic mechanisms.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CTLA-4
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The exact reason for this difference is not fully understood, but it is clear that PD-1 and CTLA-4 play biologically nonredundant roles in suppressing developing immune responses.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Of the patients who initially respond, some develop resistance at a later time and experience tumor relapse; such patients are described as having acquired resistance.”
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
“acquired resistance encompasses those cases in which patients initially responded to an ICI but later became refractory.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
In the paper
“In the subsequent phase III clinical trial, more than 30% of patients with advanced melanoma achieved an objective response following pembrolizumab monotherapy compared with 12% of patients treated with ipilimumab alone (58).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [58] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This is not surprising given that PD-L1 blockade inhibits not only the PD-1/PD-L1 axis but also PD-L1/CD80 cis interactions on DCs, freeing more CD80 molecules to enhance T cell priming (63).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [63] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Starting with the approval of anticytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4) for advancedstage melanoma in 2011”
- Also stated in: § INTRODUCTION · plain
“An antibody against cytotoxic T lymphocyte-associated protein 4 (CTLA-4) called ipilimumab was the first to receive approval for the treatment of metastatic melanoma.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § INTRODUCTION · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Beyond low mutational burden, primary resistance to checkpoint therapies can also occur if critical signaling pathways are disrupted in the tumor.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, mutations in critical antitumor pathways, such as in IFN-γ and antigen presentation, can be a source of primary resistance to ICIs.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although other potential mechanisms of acquired resistance have been proposed and examined in preclinical studies, it is clear that the difference in our understanding of primary resistance and of acquired resistance is considerable.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, as a general observation, tumor types exhibiting low tumor mutational burdens are commonly associated with resistance or nonresponsiveness to ICIs.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“However, whether the epigenetic landscape of the tumor cells or T cell exhaustion is contributing to resistance is not well understood, leaving much room for further understanding of how epigenetics can lead to nonresponse to ICIs (108, 109).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“One of the most commonly used biomarkers for predicting response to ICIs is the intensity of PD-L1 expression on tumor cells, which is positively correlated with response to ICIs in several cancer settings (74,75,80).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“For example, MEX3B, a gene responsible for downregulating MHC I expression in tumors, was expressed at higher levels in nonresponders to anti-PD-1 than in responders (96).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [96] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notwithstanding these exceptions, low mutational load, and therefore low availability of neoantigens, is a major contributor to primary resistance to ICIs.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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In the paper
“Similar disruptions in MHC I presentation in patients with lung cancer were also reported, implicating dysregulated antigen presentation as a potent mediator of acquired resistance (111).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
What the sources say
- Not checked yetcites [111] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In the same study, tumor cells in another patient demonstrating relapse contained a frameshift deletion of β 2 -microglobulin (B2M), disrupting MHC I trafficking to the cell surface and thereby rendering the tumor cells invisible to cytotoxic CD8 + T cells (110).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
What the sources say
- Not checked yetcites [110] source
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, a patient's overall microflora makeup may contribute to primary resistance, as well as response, to ICIs.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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In the paper
“In addition, fecal transplants from patients who benefitted clinically from anti-CTLA-4 therapy favored the growth of B. fragilis, linking this species with improved response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [99] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Similar findings for anti-PD-1 therapy have been reported, although different microbes have been implicated (100, 101).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Table 1, ICIs are approved for various cancer types, with anti-PD-1 antibodies having received the greatest number of approvals.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Of all the patients who met the eligibility criteria for ICI therapy in 2018, only an estimated 12.5% would have benefitted (79).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [79] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although our understanding of acquired resistance is far too undeveloped to determine whether this is the case”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One mechanism purporting to contribute to the development of acquired resistance is evolution or selection of tumors that acquire mutations in critical pathways involved in the checkpoint blockade response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In the clinic, a strong IFN-γ signature has been identified as a useful predictor and indicator of response in anti-PD-1-treated patients across various cancer indications (75,92,93).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike primary resistance to ICIs, acquired resistance, also known as secondary resistance, is not as well understood.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Acquired Resistance
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The common thread that unites these types of tumors and that potentiates their response to ICIs is their high neoantigen load, which leads to increased visibility of the tumor to the immune system and the development of a more potent antitumor T cell response following ICI treatment.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Given this contribution of mutational burden to ICI efficacy, tumors with low mutational burdens, such as prostate and pancreatic cancers, might be expected to respond poorly to ICIs, and this is indeed the case (88).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [88] source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Another well-recognized biomarker that predicts response or nonresponse to ICIs is the mutational burden of the tumor, with higher tumor mutational loads strongly associated with response to both anti-CTLA-4 and anti-PD-1 across multiple cancer indications (83)(84)(85)(86).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Newly developed autoimmune disease, such as type I diabetes in patients with no prior history of the disease, following checkpoint therapy has also been reported to occur”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies have shown an association between development of vitiligo and improved objective response rates and overall survival in patients with melanoma (124-126).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“nonresponders to PD-1 treatment exhibited lower levels of CD69 and lower production of MIP-1β by NK cells (137).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [137] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The frequency and severity of irAEs differ between different immune checkpoint modalities, with anti-PD-1 typically exhibiting a more favorable safety profile compared with anti-CTLA-4.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“anti-CTLA-4 and anti-PD-1 treatments are associated with distinct predictive biomarkers.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [137] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the favorable correlation between CD8 + PD-1 hi T cells and response to treatment was attributed not only to their tumor reactivity but also to their secretion of the chemokine CXCL13, which contributed to the recruitment of other immune cells, such as B cells and T follicular helper cells, that may participate in antitumor responses (147).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [147] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“numerous studies of ICI-treated patients have highlighted the importance of immune cells both at the tumor site and in the periphery.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [131] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Studies claiming improved outcomes associated with irAEs can be found alongside studies reporting no apparent correlation, regardless of the type of ICI used (120, 127-130).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“overactivation of the immune system to boost antitumor immunity can act as a double-edged sword, leading to the development of irAEs that can range from mild rash to severe colitis to life-threatening myocarditis (114, 115).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“These changes throughout the host were critical to the antitumor response, as administration of fingolimod, a small molecule that inhibits egress of lymphocytes from the lymph nodes, abrogated the effect of the immunotherapy.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [131] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Combination treatment of advanced melanoma with both anti-CTLA-4 and anti-PD-1 led to a marked increase in both the incidence and the severity of irAEs, with 55% of those patients exhibiting high-grade irAEs (59).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
- Not checked yetcites [59] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“approximately 10-20% experience more severe grade 3 or 4 irAEs”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In general, discontinuation of ICI therapy and subsequent treatment with immunosuppressive agents do not appear to negatively impact patient outcomes (120, 121).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“intratumoral memory-like CD8 + T cells were also more strongly associated with response to ICI therapy.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [144] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“decreased expression of PD-1 on these CD8 + T cells during therapy was a hallmark of better treatment outcome (143).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [143] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“examination of blood and tumors from patients has revealed several biomarkers that correlate with clinical outcome.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“proliferation of circulating CD8 + PD-1 hi CTLA-4 + T cells, within 3-4 weeks of ICI treatment, was also associated with responders in patients with melanoma and patients with NSCLC (148, 149).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“upon immunotherapy administration in mammary tumor-bearing mice, effective therapy was characterized by marked changes in immune cells not only in the tumor but also in peripheral organs such as the draining lymph nodes, blood, and bone marrow (131).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [131] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“30-60% of patients experience irAEs of any grade”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the frequency of CD8 + effector memory cells in the peripheral blood of patients with advanced melanoma 9 weeks after anti-CTLA-4 treatment correlated with clinical benefit and overall survival (142).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [142] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Systemic administration of ICIs impacts not just T cells but also other immune cells throughout the body.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“these sorts of invasive studies cannot be carried out in patients.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“several clinical studies of patients treated with ICIs have highlighted a potential role for CD4 + T cells in antitumor immunity.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a low absolute monocyte count in circulation is associated with better ipilimumab therapy outcome in patients with melanoma.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [135] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“many of the new posttreatment clonotypes infiltrating the tumor could be identified in the blood, implicating the importance of T cell activation in the periphery in the developing antitumor response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [164] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Balatoni et al. (153) demonstrated that patients with melanoma who exhibited a higher frequency of Tregs in lymph node metastases responded better to ipilimumab compared with patients who had fewer Tregs (133).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“ICI treatment of patients induces significant immune changes both in the periphery and in the tumor site.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“generating T cell responses to various tumor epitopes may help minimize tumor selection and eventual tumor escape.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In preclinical models, both of these innate immune cell types aid tumor growth and metastasis through their secretion of factors that suppress antitumor immune responses, especially those of CD8 + T cells and NK cells (166, 167).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“This finding suggests that, contrary to the concept of in situ reinvigoration of exhausted CD8 + T cells that was widely considered to be the mechanism of ICI therapy, an effective ICI response may actually depend on an influx of novel, less exhausted T cells into the tumor site.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [164] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“patients with castration-resistant prostate cancer or advanced melanoma who maintained their oligoclonal circulating baseline TCRs after receiving anti-CTLA-4 responded better to therapy than those in which more of those clonotypes were lost (163).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [163] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These studies also put forth the idea that assessing T cell diversity or clonality in the blood may be useful for understanding the T cell profile in the tumor, as Yost et al. and Wu et al. implicate the periphery as the source of newly infiltrated T cells in the tumor.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Overall, these studies support the concept that increased abundance of CD8 + T cells and CD8 + T cells with memory-like phenotypes in peripheral and tumor tissues prior to or after initiation of therapy is correlated with a favorable response to ICIs.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“patients who responded to anti-PD-1 demonstrated lower tumoral macrophage infiltration (161).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [161] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is clear that the frequency of CD4 + T cell populations prior to therapy and the dynamic changes they undergo during therapy can serve as important predictive biomarkers distinguishing ICI responders from nonresponders.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“CD14 + CD16 -HLA-DR hi monocytes were a strong predictor of progression-free and overall survival after treatment with anti-PD-1 antibody.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [174] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“in patients with metastatic pancreatic cancer, longer survival has been associated with lower baseline circulating clonality and a high number of expanded clones following anti-CTLA-4 treatment but not anti-PD-1 treatment (162).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [162] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a higher ratio of effector CD8 + T cells to Tregs in the tumors of previously vaccinated patients with melanoma correlated favorably with tumor necrosis (155).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [155] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In patients with basal cell carcinoma and patients with squamous cell carcinoma treated with anti-PD-1, TCR clones present in the tumor posttreatment consisted of a significant number of clones that were not present in the tumors prior to ICI therapy (164).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [164] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“numerous studies of patients with cancer have indeed found that these myeloid cell subsets, whether in the tumor or in peripheral tissues, were negatively correlated with effective ICI therapy (134, 161, 168-171).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“an abundance of Tregs in the blood of patients with melanoma at baseline correlated with a favorable outcome following ipilimumab treatment (135).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [135] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“The location and functional status of CD8 + T cells within tumors have also been correlated with ICI therapy outcome.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“responders had a higher frequency of memory CD4 + T cells, as defined by expression of CCR7, CD28, and CD62L (144).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [144] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“An early study of patients with melanoma treated with ipilimumab showed that 8-14 weeks after the first dose, a heightened frequency of CD4 + T cells in blood correlated with increased overall survival (135).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [135] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“in patients with bladder cancer, CTLA-4 blockade led to increased inducible T cell costimulator (ICOS) expression on IFN-γ producing CD4 + T cells.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [156] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“both a low baseline frequency of MDSCs and a low frequency of MDSCs in the blood of patients with melanoma following ipilimumab treatment were associated with favorable therapy outcome (134, 169-171).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“decreases in Tregs in the peripheral blood and tumors of patients with metastatic melanoma treated with ICIs have been associated with ICI response and increased patient survival”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“an increased proportion of circulating Tregs in patients with melanoma after treatment with anti-PD-1 therapy correlated with a favorable response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [154] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“lack of PD-1 downregulation on CD4 + PD-1 hi T cells following treatment with anti-PD-1 resulted in a higher risk of death in patients with advanced melanoma (152).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [152] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a decrease in the abundance of tumor-infiltrating macrophages in patients with melanoma treated with anti-CTLA-4 and anti-PD-1 antibodies distinguished responders from nonresponders (172).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [172] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“a study performed by Wu et al. (165) that similarly suggested a peripheral origin for intratumoral CD8 + clonotypes, on the basis of the presence of expanded clones infiltrating the tumor as well as normal adjacent tissue and blood.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [165] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“The increased abundance of ICOS + CD4 + T cells resulted in an increased ratio of these cells to Tregs (156) both in the tumor and in peripheral blood.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [156] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“no TCR parameters were found to be associated with clinical outcomes in patients treated with anti-PD-1.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [162] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“increased frequencies of CD62L low CD4 + T cells in the circulation of patients with NSCLC before treatment with anti-PD-1 were predictive of greater progression-free survival following ICI treatment.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [151] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“although ICIs are the most widely used, they are not the only FDA-approved immunotherapies.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CONCLUDING REMARKS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 40
- Probably not a substantial claim. 5
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Response rates to ICI treatment vary widely among different cancers, ranging from greater than 80% in patients with refractory Hodgkin's lymphoma to little or no response in patients with mismatch repair-proficient colorectal cancer (76, 77); many tumor indications fall within a response rate range of 20% to 40% (78).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Partly supportedcites [76] sourceExperimental — accuracy not yet measured
The Introduction notes activity of PD-1 blockade in classical Hodgkin lymphoma, supporting the qualitative point that it responds to treatment. It gives no response rate above 80%, and our copy does not address mismatch repair-proficient colorectal cancer (searched for that term). The 20–40% range is attached to a different citation in the citing sentence. (LLM, conf=0.78)
- Supportedcites [77] source
The Results (Primary End Point) report a 0% objective response rate in patients with mismatch repair–proficient colorectal cancer; the Radiographic Evaluation likewise reports no objective responses among 18 such patients. This supports the low-or-no-response portion of the sentence for which this paper is cited. The 20–40% statement is separately attributed to citation 78. (LLM, conf=0.92)
- Partly supportedcites [78] sourceExperimental — accuracy not yet measured
The citation to this paper is attached to the statement that many tumor indications have response rates of 20–40%. In “Clinical effects of PD-1/PD-L1 blockade therapy” (page unavailable), the paper reports 35–40% for common melanoma variants, but 15–25% for several other cancers. It supports variation across indications, not the stated range for all the examples it discusses. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
In the paper
“At the end of the trial, progression-free survival was highest in patients who received the combination therapy, followed by patients treated with nivolumab alone, and was lowest in patients treated with ipilimumab alone (59).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
- Not checked yetcites [59] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“immune-related adverse events complicate treatment.”
- Also stated in: § PD-1 and PD-L1 · plain
“a large proportion of ICI-treated patients develop immune-related adverse events (irAEs), some of which can be life-threatening.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § PD-1 and PD-L1 · plain
None of the sources cited for this claim have been checked yet.
In the paper
“Once TCR signaling is induced, intracellularly stored CTLA-4 molecules traffic to the cell surface, where they can bind and compete for the same ligands as CD28, but with greater affinity, thereby dampening costimulation (7,8).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CTLA-4
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Although PD-1 is expressed on the surface of most activated immune cells, such as macrophages, dendritic cells (DCs), Langerhans cells, B cells, and T cells, its expression is most highly upregulated on exhausted T cells (34,35).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ICIs-which now also include antibodies against programmed cell death 1 (PD-1) and its ligand (PD-L1)-quickly gained US Food and Drug Administration approval for the treatment of a wide array of cancer types, demonstrating unprecedented extension of patient survival.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Abstract
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“CTLA-4, an inhibitory receptor expressed primarily by T cells, functions to dampen T cell activity and is upregulated upon T cell activation (1)(2)(3).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CTLA-4
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“ICIs work by releasing the inhibitory brakes of T cells, resulting in robust activation of the immune system and productive antitumor immune responses.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Subsequent human studies have consistently shown that PD-L1 and PD-L2 expression not only increases in cancerous tissues but is also linked to poor disease prognosis in many cancer types (50)(51)(52)(53)(54)(55)(56).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Patients who never experience a therapeutic response are described as having primary resistance.”
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
“Primary resistance refers to those cases in which no initial response to checkpoint therapy was observed”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > INTRODUCTION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This stratification in progression-free survival hinted at the possibility of combining ICIs to achieve maximum antitumor efficacy.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Critically, analogous to what was observed in preclinical studies, the 20% of patients whose tumors were completely cleared maintained their response for the duration of the study, with a median follow-up time of approximately 30 months.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CTLA-4
What the sources say
- Not checked yetcites [32] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Even among patients with melanoma, which has one of the highest rates of response to ICI, 60-70% of patients do not experience an objective response to anti-PD-1 therapy; of those that do, 20-30% demonstrate eventual tumor relapse and progression (74,75).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > RESISTANCE TO IMMUNE CHECKPOINT INHIBITORS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, in preclinical models, the therapeutic response to anti-CTLA-4 therapy was found to be dependent on Bacteroides species, as germfree mice or antibiotic-treated mice did not respond to anti-CTLA-4, but response was rescued through gavage of Bacteroides fragilis (99).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [99] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, PD-L1-negative tumors can still occasionally respond to anti-PD-1 therapy, and high PD-L1 expression, although correlative, is by no means sufficient for generating a response following anti-PD-1 therapy, indicating that other factors are involved in determining response and nonresponse to ICIs (80)(81)(82).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The underlying cause of the high mutational burden is not important for determining whether a tumor will respond to ICIs, as melanoma and NSCLC, which acquire mutations through UV-and carcinogen-induced DNA damage, respectively, respond just as well to ICIs as do tumors that acquire mutations through genomic instability or deficient mismatch repair (74,80,87).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In another study, MHC I downregulation via transcriptional repression was associated with primary resistance to anti-CTLA-4 therapy but not to anti-PD-1 therapy, and the response to anti-PD-1 was more dependent on MHC II expression linked to an IFN-γ-regulated module of genes (97).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
- Not checked yetcites [97] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Some patients who receive ICIs do not respond to treatment (primary resistance), while others respond to initial therapy but eventually relapse (acquired resistance).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Figure 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Several studies have demonstrated that mutations in genes involved in the SWI-SNF chromatin remodeling complex may sensitize human tumors to ICIs and that treatment with an epigenetic modulator can potentiate the ICI-mediated antitumor response through increased production of chemokines responsible for recruiting CD8 + T cells (104-107).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Apart from atezolizumab, durvalumab and avelumab are also approved for use in patients with urothelial carcinoma (70)(71)(72), and avelumab is approved for use in patients with Merkel cell carcinoma (73).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > PD-1 and PD-L1
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, it stands to reason that tumors with absent or low expression of PD-L1 are more likely to exhibit resistance to anti-PD-1 and anti-PD-L1 therapies, and this assertion is supported by response rates of only up to 10% in patients with PD-L1-low melanoma and patients with NSCLC treated with anti-PD-1 compared with 40-50% in patients with high PD-L1 expression (74,80).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This idea is further supported by reports of decreased overall survival and progression-free survival in ICI-treated patients who received antibiotics (101-103).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Interferon-γ (IFN-γ) is an important cytokine for initiating and maintaining a potent antitumor response not only through promoting CD8 + cytotoxic T cell activity and skewing toward a Th1 response but also through exerting antiproliferative, proapoptotic effects and inducing major histocompatibility complex class I (MHC I) upregulation in tumor cells (90,91).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Primary Resistance
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“the presence of CD8 + PD-1 hi T cells in the tumors of patients with melanoma and patients with NSCLC prior to anti-PD-1 administration was predictive of treatment response and correlated with overall survival (146, 147).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In patients with untreated melanoma, treatment with anti-CTLA-4 led to grade 3 or 4 irAEs in 27.3% of patients and treatment with anti-PD-1 led to such severe irAEs in only 16.3% of patients (59).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
- Not checked yetcites [59] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This association may be stronger than those with other irAE manifestations due to the autoimmune reaction targeting shared antigens between healthy melanocytes and the melanoma cells, allowing the occurrence of vitiligo to serve as a surrogate measure of the developing antitumor response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although significant effort has been devoted to understanding the mechanisms of primary resistance, studies of acquired resistance have begun only recently.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Figure 1
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“increased lymphocyte counts in the blood are associated not only with favorable treatment outcome but also with increased overall survival in patients with melanoma treated with ICIs (132-135).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, there are exceptions, indicating that better understanding of the interplay between the developing antitumor response following ICI therapy and the use of immunosuppressive agents is needed (117, 122, 123).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a subset of peripheral effector-memorylike CD4 + T cells was associated with effective immunotherapy and could initiate an antitumor response upon adoptive transfer to untreated tumor-bearing mice (131).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [131] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Whereas CD45RA + naive CD8 + T cells negatively correlated with response with ipilimumab treatment, CD45RA -CD8 + T cells and CD8 + T effector memory cells (CD45RA -CCR7 -) were more abundant in responsive patients (137).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [137] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“anti-CTLA-4 resulting in more hypophysitis and more severe colitis cases and anti-PD-1 resulting in more pneumonitis, thyroiditis, and nephritis cases (114, 118).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“These differences may be the result of the different mechanisms of T cell inhibition by CTLA-4 and PD-1, as the former is understood to function more proximally to T cell activation and the latter is thought to function at later stages in the periphery (119).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > IMMUNE-RELATED ADVERSE EVENTS
What the sources say
- Not checked yetcites [119] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The tumor rejection phase was characterized by proliferating immune cells in the draining lymph nodes but not in the tumor, suggesting that the immune response in the periphery is important for maintaining and activating immune cells participating in the antitumor response.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [131] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a higher frequency of memory CD45RA -CD4 + T cells in the blood of patients with melanoma at baseline was associated with a favorable response to ipilimumab, whereas an increased presence of naive CD45RA + CD4 + T cells correlated with nonresponders (137).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [137] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“some studies have found that high TCR diversity in peripheral blood and tumors prior to ICI therapy is predictive of effective treatment, others have pointed to ICI therapy-associated increases in TCR clonality, that is, enrichment of T cells with the same TCRs, as a sign of effective therapy (150, 157-161).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is unlikely that quantifying a single cell population or parameter will accurately predict response or nonresponse to ICI treatment, and a more holistic approach encompassing multiple cell types will be necessary.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Controversial results
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“this study nonetheless points to the possibility that ICI therapy brings about similar tumoral and systemic changes in immune cells, suggesting that circulating immune cells may provide a window into changes in immune cells in the tumor.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“One study, for example, has suggested that anti-CTLA-4 induces mainly proliferation of ICOS + CD4 + effector T cells and that anti-PD-1 is associated primarily with reinvigoration CD8 + PD-1 hi T cells (175).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > Controversial results
What the sources say
- Not checked yetcites [175] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas the negative role for tissue macrophages and MDSCs in ICI treatment is well established, our understanding of the role of circulating monocytes remains blurred.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“an increased frequency of circulating monocytes at baseline, unlike macrophages and MDSCs in tumors and other tissues, predicts superior ICI responses (174).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > LOCAL AND SYSTEMIC IMMUNE RESPONSES TO IMMUNE CHECKPOINT INHIBITORS
What the sources say
- Not checked yetcites [174] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A DC vaccine for the treatment of advanced prostate cancer and chimeric antigen receptor T cells for the treatment of several hematological malignancies are among other immunotherapies that have also received FDA approval (176, 177).”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CONCLUDING REMARKS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“the role of systemic immunity is not well understood in these modalities.”
§ Annual Review of Pathology: Mechanisms of Disease Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance > CONCLUDING REMARKS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper relies on this without support.
Lymphocytes, especially CD8+ T cells and NK cells, are critical for antitumor immunity.
“A paradigm in the field of tumor immunology is that lymphocytes, especially CD8 + T cells and NK cells, are critical for antitumor immunity.”
The paper relies on this without support.
For any T cell to become activated and acquire effector functions, its TCR must recognize its cognate antigen presented on an MHC molecule.
“For any T cell to become activated and acquire effector functions, its TCR must recognize its cognate antigen presented on an MHC molecule.”
The paper relies on this without support.
The antigen specificity of a T cell is determined by its TCR, and each cell expresses multiple copies of only a single TCR, making T cells highly specific.
“The antigen specificity of a T cell is determined by its TCR, and because each cell expresses multiple copies of only a single TCR, T cells are highly specific in their response.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Preclinical studies emphasizing the pivotal role of the PD-1/PD-L1 axis in suppressing effector T cell function led to FDA approval of nivolumab and pembrolizumab, monoclonal antibodies to PD-1, for various solid immunologically ‘hot’ cancers like melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (Bagchi et al., 2021).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Bagchi et al., 2021
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Ipilimumab, the first FDA-approved monoclonal antibody targeting the negative immune checkpoint protein CTLA-4, enhances T cell activation and depletes Tregs in the tumor bed (Bagchi et al., 2021).”
From Microphysiological systems as models for immunologically ‘cold’ tumors (2024) · cites this paper as Bagchi et al., 2021
Experimental — accuracy not yet measuredIn the citing paper
“Some studies reported that there might be phosphotyrosine‐independent cooperation among SHP2 and CTLA4 as alternated tyrosine CTLA4 could interact with SHP2 and inhibit TCRζ signaling pathways [299, 300].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [299]
Citations
Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer
Reck, M., Rodríguez-Abreu, D., Robinson, A. G., Hui, R., Csőszi, T., Fülöp, A., Gottfried, M., Peled, N., Tafreshi, A., Cuffe, S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606774 · Cited by 10,089
PD-1 Blockade in Tumors with Mismatch-Repair Deficiency
Le, D. T., Uram, J. N., Wang, H., Bartlett, B. R., Kemberling, H., Eyring, A. D., Skora, A. D., Luber, B. S., Azad, N. S., Laheru, D., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1500596 · Cited by 9,377
Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer
Rizvi, N. A., Hellmann, M. D., Snyder, A., Kvistborg, P., Makarov, V., Havel, J. J., Lee, W., Yuan, J., Wong, P., Ho, T. S., et al. (2015) · Science · doi:10.1126/science.aaa1348 · Cited by 7,802
Cancer immunotherapy using checkpoint blockade
Ribas, A., & Wolchok, J. D. (2018) · Science · doi:10.1126/science.aar4060 · Cited by 6,791
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Garon, E. B., Rizvi, N. A., Hui, R., Leighl, N., Balmanoukian, A. S., Eder, J. P., Patnaik, A., Aggarwal, C., Gubens, M., Horn, L., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1501824 · Cited by 6,198
Pembrolizumab versus Ipilimumab in Advanced Melanoma
Robert, C., Schachter, J., Long, G. V., Arance, A., Grob, J. J., Mortier, L., Daud, A., Carlino, M. S., McNeil, C., Lotem, M., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1503093 · Cited by 5,887
Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors
Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P. M., Alou, M. T., Daillère, R., Fluckiger, A., Messaoudene, M., Rauber, C., Roberti, M. P., et al. (2018) · Science · doi:10.1126/science.aan3706 · Cited by 5,671
Research works printed but not linked: 1
- Yang YF, 1997, Cancer Res, 57, 4036
Cited by
Sorted by citations
Radiotherapy combined with immunotherapy: the dawn of cancer treatment
Zhang, Z., Liu, X., Chen, D., & Yu, J. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01102-y · Cited by 736
Tumor-infiltrating regulatory T cells as targets of cancer immunotherapy
Tay, C., Tanaka, A., & Sakaguchi, S. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.014 · Cited by 614
Therapeutic cancer vaccines: Advancements, challenges, and prospects
Fan, T., Zhang, M., Yang, J., Zhu, Z., Cao, W., & Dong, C. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01674-3 · Cited by 597
Wang, S., Wang, J., Chen, Z., Luo, J., Guo, W., Sun, L., & Lin, L. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00522-z · Cited by 657
Shaping Polarization Of Tumor-Associated Macrophages In Cancer Immunotherapy
Gao, J., Liang, Y., & Wang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.888713 · Cited by 586
Metadata
- Authors
- Bagchi, S., Yuan, R., & Engleman, E. G.
- Affiliations
- Stanford Medicine (US)
- Venue
- Annual Review of Pathology: Mechanisms of Disease
- Publisher
- Annual Reviews
- Published
- 2021-01-24
- Volume
- 16
- Issue
- 1
- Pages
- 223-249
- ISSN
- 1553-4006 (ISSN-L)
- 1553-4014
- OpenAlex
- W3106005610
- Semantic Scholar
- 58a498a336df510986c6c2190384da22c7b34f10
- Cited by
- 2,189
- References
- 176
- Citations by year
- 2026: 259 · 2025: 425 · 2024: 548 · 2023: 514 · 2022: 377 · 2021: 64
- FWCI
- 25.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annual Review of Pathology Mechanisms of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (R01CA233958, U54CA209971, R01CA222969)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- immune checkpoint inhibitors, cancer immunotherapy, CTLA-4, PD-1, PD-L1, immune resistance mechanisms, immune-related adverse events, antitumor immunity, combination immunotherapy, melanoma
- MeSH terms
- Immune Checkpoint Inhibitors, Animals, Humans, Immunotherapy, Neoplasms, Drug Resistance, Neoplasm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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