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.
Overview
Integrity signals
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Cites
Statistics
Verification
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.
- Load-bearing: passes — The paper’s conclusions depend on it.
- 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.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- 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.
- 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
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Charoentong, P., Finotello, F., Angelova, M., Mayer, C., Efremova, M., Rieder, D., Hackl, H., & Trajanoski, Z. (2017) · Cell Reports · doi:10.1016/j.celrep.2016.12.019 · Cited by 5,041
Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D., Hoffman, K., Wei, S. C., et al. (2018) · Science · doi:10.1126/science.aan4236 · Cited by 4,812
Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer
Schmid, P., Adams, S., Rugo, H. S., Schneeweiss, A., Barrios, C. H., Iwata, H., Diéras, V., Hegg, R., Im, S.-A., Shaw Wright, G., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1809615 · Cited by 4,350
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
Enhancement of Antitumor Immunity by CTLA-4 Blockade
Leach, D. R., Krummel, M. F., & Allison, J. P. (1996) · Science · doi:10.1126/science.271.5256.1734 · Cited by 3,955
IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade
Ayers, M., Lunceford, J., Nebozhyn, M., Murphy, E., Loboda, A., Kaufman, D. R., Albright, A., Cheng, J. D., Kang, S. P., Shankaran, V., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci91190 · Cited by 3,788
Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC
Socinski, M. A., Jotte, R. M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N., Rodríguez-Abreu, D., Moro-Sibilot, D., Thomas, C. A., Barlesi, F., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716948 · Cited by 3,733
Rosenberg, J. E., Hoffman-Censits, J., Powles, T., van der Heijden, M. S., Balar, A. V., Necchi, A., Dawson, N., O'Donnell, P. H., Balmanoukian, A., Loriot, Y., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00561-4 · Cited by 3,669
First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer
Horn, L., Mansfield, A. S., Szczęsna, A., Havel, L., Krzakowski, M., Hochmair, M. J., Huemer, F., Losonczy, G., Johnson, M. L., Nishio, M., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1809064 · Cited by 3,586
Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota
Vétizou, M., Pitt, J. M., Daillère, R., Lepage, P., Waldschmitt, N., Flament, C., Rusakiewicz, S., Routy, B., Roberti, M. P., Duong, C. P. M., et al. (2015) · Science · doi:10.1126/science.aad1329 · Cited by 3,488
Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192461099 · Cited by 3,261
Ishida, Y., Agata, Y., Shibahara, K., & Honjo, T. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05481.x · Cited by 3,259
Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma
Zaretsky, J. M., Garcia-Diaz, A., Shin, D. S., Escuin-Ordinas, H., Hugo, W., Hu-Lieskovan, S., Torrejon, D. Y., Abril-Rodriguez, G., Sandoval, S., Barthly, L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1604958 · Cited by 3,237
CTLA-4 Control over Foxp3 + Regulatory T Cell Function
Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., & Sakaguchi, S. (2008) · Science · doi:10.1126/science.1160062 · Cited by 2,956
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Tivol, E. A., Borriello, F., Schweitzer, A. N., Lynch, W. P., Bluestone, J. A., & Sharpe, A. H. (1995) · Immunity · doi:10.1016/1074-7613(95)90125-6 · Cited by 2,914
Genomic correlates of response to CTLA-4 blockade in metastatic melanoma
Van Allen, E. M., Miao, D., Schilling, B., Shukla, S. A., Blank, C., Zimmer, L., Sucker, A., Hillen, U., Geukes Foppen, M. H., Goldinger, S. M., et al. (2015) · Science · doi:10.1126/science.aad0095 · Cited by 2,839
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999) · Immunity · doi:10.1016/s1074-7613(00)80089-8 · Cited by 2,749
Tumor and Microenvironment Evolution during Immunotherapy with Nivolumab
Riaz, N., Havel, J. J., Makarov, V., Desrichard, A., Urba, W. J., Sims, J. S., Hodi, F. S., Martín-Algarra, S., Mandal, R., Sharfman, W. H., et al. (2017) · Cell · doi:10.1016/j.cell.2017.09.028 · Cited by 2,401
CTLA-4 and PD-1 Pathways: Similarities, Differences, and Implications of Their Inhibition
Buchbinder, E. I., & Desai, A. (2016) · American Journal of Clinical Oncology · doi:10.1097/coc.0000000000000239 · Cited by 2,360
Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance
Martins, F., Sofiya, L., Sykiotis, G. P., Lamine, F., Maillard, M., Fraga, M., Shabafrouz, K., Ribi, C., Cairoli, A., Guex-Crosier, Y., et al. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-019-0218-0 · Cited by 2,314
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy
Cristescu, R., Mogg, R., Ayers, M., Albright, A., Murphy, E., Yearley, J., Sher, X., Liu, X. Q., Lu, H., Nebozhyn, M., et al. (2018) · Science · doi:10.1126/science.aar3593 · Cited by 2,301
Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers
Goodman, A. M., Kato, S., Bazhenova, L., Patel, S. P., Frampton, G. M., Miller, V., Stephens, P. J., Daniels, G. A., & Kurzrock, R. (2017) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0386 · Cited by 2,264
CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation.
Krummel, M. F., & Allison, J. P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.2.459 · Cited by 2,245
Takahashi, T., Tagami, T., Yamazaki, S., Uede, T., Shimizu, J., Sakaguchi, N., Mak, T. W., & Sakaguchi, S. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.303 · Cited by 2,233
CTLA-4 can function as a negative regulator of T cell activation
Walunas, T. L., Lenschow, D. J., Bakker, C. Y., Linsley, P. S., Freeman, G. J., Green, J. M., Thompson, C. B., & Bluestone, J. A. (1994) · Immunity · doi:10.1016/1074-7613(94)90071-x · Cited by 2,222
Read, S., Malmström, V., & Powrie, F. M. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.2.295 · Cited by 2,206
Effector Memory T Cells, Early Metastasis, and Survival in Colorectal Cancer
Pagès, F., Berger, A., Camus, M., Sanchez-Cabo, F., Costes, A., Molidor, R., Mlecnik, B., Kirilovsky, A., Nilsson, M., Damotte, D., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa051424 · Cited by 2,135
Neoadjuvant PD-1 Blockade in Resectable Lung Cancer
Forde, P. M., Chaft, J. E., Smith, K. N., Anagnostou, V., Cottrell, T. R., Hellmann, M. D., Zahurak, M., Yang, S. C., Jones, D. R., Broderick, S., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1716078 · Cited by 2,099
Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma
Sade-Feldman, M., Yizhak, K., Bjorgaard, S. L., Ray, J. P., de Boer, C. G., Jenkins, R. W., Lieb, D. J., Chen, J. H., Frederick, D. T., Barzily-Rokni, M., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.038 · Cited by 2,053
Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice
Nishimura, H., Okazaki, T., Tanaka, Y., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Mizoguchi, A., Hiai, H., Minato, N., et al. (2001) · Science · doi:10.1126/science.291.5502.319 · Cited by 1,868
Robert, C., Ribas, A., Wolchok, J. D., Hodi, F. S., Hamid, O., Kefford, R., Weber, J. S., Joshua, A. M., Hwu, W.-J., Gangadhar, T. C., et al. (2014) · The Lancet · doi:10.1016/s0140-6736(14)60958-2 · Cited by 1,774
Ahmadzadeh, M., Johnson, L. A., Heemskerk, B., Wunderlich, J. R., Dudley, M. E., White, D. E., & Rosenberg, S. A. (2009) · Blood · doi:10.1182/blood-2008-12-195792 · Cited by 1,766
CTLA-4 is a second receptor for the B cell activation antigen B7.
Linsley, P. S., Brady, W., Urnes, M., Grosmaire, L. S., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of experimental medicine · doi:10.1084/jem.174.3.561 · Cited by 1,685
Siddiqui, I., Schaeuble, K., Chennupati, V., Fuertes Marraco, S. A., Calderon-Copete, S., Pais Ferreira, D., Carmona, S. J., Scarpellino, L., Gfeller, D., Pradervand, S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.021 · Cited by 1,679
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response
Huang, A. C., Postow, M. A., Orlowski, R. J., Mick, R., Bengsch, B., Manne, S., Xu, W., Harmon, S., Giles, J. R., Wenz, B., et al. (2017) · Nature · doi:10.1038/nature22079 · Cited by 1,664
West, H., McCleod, M., Hussein, M., Morabito, A., Rittmeyer, A., Conter, H. J., Kopp, H.-G., Daniel, D., McCune, S., Mekhail, T., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30167-6 · Cited by 1,662
Clonal replacement of tumor-specific T cells following PD-1 blockade
Yost, K. E., Satpathy, A. T., Wells, D. K., Qi, Y., Wang, C., Kageyama, R., McNamara, K. L., Granja, J. M., Sarin, K. Y., Brown, R. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0522-3 · Cited by 1,534
Haslam, A., & Prasad, V. (2019) · JAMA Network Open · doi:10.1001/jamanetworkopen.2019.2535 · Cited by 1,413
Hamanishi, J., Mandai, M., Iwasaki, M., Okazaki, T., Tanaka, Y., Yamaguchi, K., Higuchi, T., Yagi, H., Takakura, K., Minato, N., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611533104 · Cited by 1,378
Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade
Pauken, K. E., Sammons, M. A., Odorizzi, P. M., Manne, S., Godec, J., Khan, O., Drake, A. M., Chen, Z., Sen, D. R., Kurachi, M., et al. (2016) · Science · doi:10.1126/science.aaf2807 · Cited by 1,348
Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations
Shin, D. S., Zaretsky, J. M., Escuin-Ordinas, H., Garcia-Diaz, A., Hu-Lieskovan, S., Kalbasi, A., Grasso, C. S., Hugo, W., Sandoval, S., Torrejon, D. Y., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-1223 · Cited by 1,337
Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
Curiel, T. J., Wei, S., Dong, H., Alvarez, X., Cheng, P., Mottram, P., Krzysiek, R., Knutson, K. L., Daniel, B., Zimmermann, M. C., et al. (2003) · Nature Medicine · doi:10.1038/nm863 · Cited by 1,314
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade
Wei, S. C., Levine, J. H., Cogdill, A. P., Zhao, Y., Anang, N.-A. A. S., Andrews, M. C., Sharma, P., Wang, J., Wargo, J. A., Pe’er, D., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.024 · Cited by 1,302
Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy
Gao, J., Shi, L. Z., Zhao, H., Chen, J., Xiong, L., He, Q., Chen, T., Roszik, J., Bernatchez, C., Woodman, S. E., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.069 · Cited by 1,300
McDermott, D. F., Huseni, M. A., Atkins, M. B., Motzer, R. J., Rini, B. I., Escudier, B., Fong, L., Joseph, R. W., Pal, S. K., Reeves, J. A., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0053-3 · Cited by 1,260
Kaufman, H. L., Russell, J., Hamid, O., Bhatia, S., Terheyden, P., D'Angelo, S. P., Shih, K. C., Lebbé, C., Linette, G. P., Milella, M., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30364-3 · Cited by 1,236
Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy
Peng, D., Kryczek, I., Nagarsheth, N., Zhao, L., Wei, S., Wang, W., Sun, Y., Zhao, E., Vatan, L., Szeliga, W., et al. (2015) · Nature · doi:10.1038/nature15520 · Cited by 1,201
Marcus, L., Lemery, S. J., Keegan, P., & Pazdur, R. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-4070 · Cited by 1,176
Thommen, D. S., Koelzer, V. H., Herzig, P., Roller, A., Trefny, M., Dimeloe, S., Kiialainen, A., Hanhart, J., Schill, C., Hess, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0057-z · Cited by 1,161
Safety Profile of Nivolumab Monotherapy: A Pooled Analysis of Patients With Advanced Melanoma
Weber, J. S., Hodi, F. S., Wolchok, J. D., Topalian, S. L., Schadendorf, D., Larkin, J., Sznol, M., Long, G. V., Li, H., Waxman, I. M., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2015.66.1389 · Cited by 1,158
Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors
Das, S., & Johnson, D. B. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0805-8 · Cited by 1,145
Linsley, P. S., Brady, W., Grosmaire, L. S., Aruffo, A. A., Damle, N. K., & Ledbetter, J. A. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.173.3.721 · Cited by 1,126
Horvat, T. Z., Adel, N. G., Dang, T.-O., Momtaz, P., Postow, M. A., Callahan, M. K., Carvajal, R. D., Dickson, M. A., D'Angelo, S. P., Woo, K. M., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2015.60.8448 · Cited by 1,064
Gide, T. N., Quek, C., Menzies, A. M., Tasker, A. T., Shang, P., Holst, J., Madore, J., Lim, S. Y., Velickovic, R., Wongchenko, M., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.003 · Cited by 1,047
van Elsas, A., Hurwitz, A. A., & Allison, J. P. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.190.3.355 · Cited by 1,020
Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity
Hirano, F., Kaneko, K., Tamura, H., Dong, H., Wang, S., Ichikawa, M., Rietz, C., Flies, D. B., Lau, J. S., Zhu, G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.1089.65.3 · Cited by 1,018
Ott, P. A., Bang, Y.-J., Piha-Paul, S. A., Razak, A. R. A., Bennouna, J., Soria, J.-C., Rugo, H. S., Cohen, R. B., O’Neil, B. H., Mehnert, J. M., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2018.78.2276 · Cited by 969
Garris, C. S., Arlauckas, S. P., Kohler, R. H., Trefny, M. P., Garren, S., Piot, C., Engblom, C., Pfirschke, C., Siwicki, M., Gungabeesoon, J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.09.024 · Cited by 966
Systemic Immunity Is Required for Effective Cancer Immunotherapy
Spitzer, M. H., Carmi, Y., Reticker-Flynn, N. E., Kwek, S. S., Madhireddy, D., Martins, M. M., Gherardini, P. F., Prestwood, T. R., Chabon, J., Bendall, S. C., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.022 · Cited by 963
Self-citationEvolution of Neoantigen Landscape during Immune Checkpoint Blockade in Non–Small Cell Lung Cancer
Anagnostou, V., Smith, K. N., Forde, P. M., Niknafs, N., Bhattacharya, R., White, J. R., Zhang, T., Adleff, V., Phallen, J. A., Wali, N., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0828 · Cited by 918
B70 antigen is a second ligand for CTLA-4 and CD28
Azuma, M., Ito, D., Yagita∥, H., Okumura, K., Phillips, J. H., Lanier, L. L., & Somoza, C. (1993) · Nature · doi:10.1038/366076a0 · Cited by 910
Derosa, L., Hellmann, M. D., Spaziano, M., Halpenny, D., Fidelle, M., Rizvi, H., Long, N., Plodkowski, A. J., Arbour, K. C., Chaft, J. E., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdy103 · Cited by 908
Nomi, T., Sho, M., Akahori, T., Hamada, K., Kubo, A., Kanehiro, H., Nakamura, S., Enomoto, K., Yagita, H., Azuma, M., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2746 · Cited by 889
Okazaki, T., Maeda, A., Nishimura, H., Kurosaki, T., & Honjo, T. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.231486598 · Cited by 873
Thompson, R. H., Kuntz, S. M., Leibovich, B. C., Dong, H., Lohse, C. M., Webster, W. S., Sengupta, S., Frank, I., Parker, A. S., Zincke, H., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4303 · Cited by 869
Powles, T., O'Donnell, P. H., Massard, C., Arkenau, H.-T., Friedlander, T. W., Hoimes, C. J., Lee, J. L., Ong, M., Sridhar, S. S., Vogelzang, N. J., et al. (2017) · JAMA Oncology · doi:10.1001/jamaoncol.2017.2411 · Cited by 869
Freeman-Keller, M., Kim, Y., Cronin, H., Richards, A., Gibney, G., & Weber, J. S. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1136 · Cited by 863
Roh, W., Chen, P.-L., Reuben, A., Spencer, C. N., Prieto, P. A., Miller, J. P., Gopalakrishnan, V., Wang, F., Cooper, Z. A., Reddy, S. M., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah3560 · Cited by 859
Kamphorst, A. O., Pillai, R. N., Yang, S., Nasti, T. H., Akondy, R. S., Wieland, A., Sica, G. L., Yu, K., Koenig, L., Patel, N. T., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1705327114 · Cited by 854
A major chromatin regulator determines resistance of tumor cells to T cell–mediated killing
Pan, D., Kobayashi, A., Jiang, P., Ferrari de Andrade, L., Tay, R. E., Luoma, A. M., Tsoucas, D., Qiu, X., Lim, K., Rao, P., et al. (2018) · Science · doi:10.1126/science.aao1710 · Cited by 852
Ohigashi, Y., Sho, M., Yamada, Y., Tsurui, Y., Hamada, K., Ikeda, N., Mizuno, T., Yoriki, R., Kashizuka, H., Yane, K., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-04-1469 · Cited by 796
Sheppard, K.-A., Fitz, L. J., Lee, J. M., Benander, C., George, J. A., Wooters, J., Qiu, Y., Jussif, J. M., Carter, L. L., Wood, C. R., et al. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.07.083 · Cited by 791
Gettinger, S., Choi, J., Hastings, K., Truini, A., Datar, I., Sowell, R., Wurtz, A., Dong, W., Cai, G., Melnick, M. A., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0593 · Cited by 787
Thompson, R. H., Gillett, M. D., Cheville, J. C., Lohse, C. M., Dong, H., Webster, W. S., Krejci, K. G., Lobo, J. R., Sengupta, S., Chen, L., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406351101 · Cited by 776
Blank, C., Brown, I., Peterson, A. C., Spiotto, M., Iwai, Y., Honjo, T., & Gajewski, T. F. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3259 · Cited by 772
Peripheral T cell expansion predicts tumour infiltration and clinical response
Wu, T. D., Madireddi, S., de Almeida, P. E., Banchereau, R., Chen, Y.-J. J., Chitre, A. S., Chiang, E. Y., Iftikhar, H., O’Gorman, W. E., Au-Yeung, A., et al. (2020) · Nature · doi:10.1038/s41586-020-2056-8 · Cited by 770
Immune checkpoint inhibitors of PD-L1 as cancer therapeutics
Akinleye, A., & Rasool, Z. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0779-5 · Cited by 760
T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.
Linsley, P. S., Clark, E. A., & Ledbetter, J. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.13.5031 · Cited by 749
High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy
Krieg, C., Nowicka, M., Guglietta, S., Schindler, S., Hartmann, F. J., Weber, L. M., Dummer, R., Robinson, M. D., Levesque, M. P., & Becher, B. (2018) · Nature Medicine · doi:10.1038/nm.4466 · Cited by 735
Turning the corner on therapeutic cancer vaccines
Hollingsworth, R. E., & Jansen, K. (2019) · npj Vaccines · doi:10.1038/s41541-019-0103-y · Cited by 689
Molecular Basis of T Cell Inactivation by CTLA-4
Lee, K.-M., Chuang, E., Griffin, M., Khattri, R., Hong, D. K., Zhang, W., Straus, D., Samelson, L. E., Thompson, C. B., & Bluestone, J. A. (1998) · Science · doi:10.1126/science.282.5397.2263 · Cited by 684
Daud, A. I., Wolchok, J. D., Robert, C., Hwu, W.-J., Weber, J. S., Ribas, A., Hodi, F. S., Joshua, A. M., Kefford, R., Hersey, P., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.2477 · Cited by 665
Hua, C., Boussemart, L., Mateus, C., Routier, E., Boutros, C., Cazenave, H., Viollet, R., Thomas, M., Roy, S., Benannoune, N., et al. (2016) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.2707 · Cited by 655
Hodi, F. S., Butler, M., Oble, D. A., Seiden, M. V., Haluska, F. G., Kruse, A., MacRae, S., Nelson, M., Canning, C., Lowy, I., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712237105 · Cited by 650
Clinical lessons learned from the first leg of the CAR T cell journey
Majzner, R. G., & Mackall, C. L. (2019) · Nature Medicine · doi:10.1038/s41591-019-0564-6 · Cited by 636
Teulings, H.-E., Limpens, J., Jansen, S. N., Zwinderman, A. H., Reitsma, J. B., Spuls, P. I., & Luiten, R. M. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.57.4756 · Cited by 625
Downey, S. G., Klapper, J. A., Smith, F. O., Yang, J. C., Sherry, R. M., Royal, R. E., Kammula, U. S., Hughes, M. S., Allen, T. E., Levy, C. L., et al. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-0187 · Cited by 624
PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer
Yearley, J. H., Gibson, C., Yu, N., Moon, C., Murphy, E., Juco, J., Lunceford, J., Cheng, J., Chow, L. Q. M., Seiwert, T. Y., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1761 · Cited by 594
Patel, M. R., Ellerton, J., Infante, J. R., Agrawal, M., Gordon, M., Aljumaily, R., Britten, C. D., Dirix, L., Lee, K.-W., Taylor, M., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30900-2 · Cited by 590
Apolo, A. B., Infante, J. R., Balmanoukian, A., Patel, M. R., Wang, D., Kelly, K., Mega, A. E., Britten, C. D., Ravaud, A., Mita, A. C., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.6795 · Cited by 585
Rodig, S. J., Gusenleitner, D., Jackson, D. G., Gjini, E., Giobbie-Hurder, A., Jin, C., Chang, H., Lovitch, S. B., Horak, C., Weber, J. S., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aar3342 · Cited by 579
Thompson, R. H., Dong, H., Lohse, C. M., Leibovich, B. C., Blute, M. L., Cheville, J. C., & Kwon, E. D. (2007) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-2599 · Cited by 569
Maleki Vareki, S. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0479-7 · Cited by 569
Shen, J., Ju, Z., Zhao, W., Wang, L., Peng, Y., Ge, Z., Nagel, Z. D., Zou, J., Wang, C., Kapoor, P., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0012-z · Cited by 562
Meyer, C., Cagnon, L., Costa-Nunes, C. M., Baumgaertner, P., Montandon, N., Leyvraz, L., Michielin, O., Romano, E., & Speiser, D. E. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-013-1508-5 · Cited by 560
Regulation of T Cell Receptor Signaling by Tyrosine Phosphatase SYP Association with CTLA-4
Marengère, L. E. M., Waterhouse, P., Duncan, G. S., Mittrücker, H.-W., Feng, G.-S., & Mak, T. W. (1996) · Science · doi:10.1126/science.272.5265.1170 · Cited by 551
Liakou, C. I., Kamat, A., Tang, D. N., Chen, H., Sun, J., Troncoso, P., Logothetis, C., & Sharma, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806075105 · Cited by 549
Martens, A., Wistuba-Hamprecht, K., Foppen, M. G., Yuan, J., Postow, M. A., Wong, P., Romano, E., Khammari, A., Dreno, B., Capone, M., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-2412 · Cited by 541
Patsoukis, N., Brown, J., Petkova, V., Liu, F., Li, L., & Boussiotis, V. A. (2012) · Science Signaling · doi:10.1126/scisignal.2002796 · Cited by 529
Iwai, Y. (2004) · International Immunology · doi:10.1093/intimm/dxh194 · Cited by 527
Tumor immune profiling predicts response to anti–PD-1 therapy in human melanoma
Daud, A. I., Loo, K., Pauli, M. L., Sanchez-Rodriguez, R., Sandoval, P. M., Taravati, K., Tsai, K., Nosrati, A., Nardo, L., Alvarado, M. D., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci87324 · Cited by 525
Ostrand-Rosenberg, S., & Fenselau, C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701019 · Cited by 509
Nishimura, H. (1998) · International Immunology · doi:10.1093/intimm/10.10.1563 · Cited by 500
Faje, A. T., Lawrence, D., Flaherty, K., Freedman, C., Fadden, R., Rubin, K., Cohen, J., & Sullivan, R. J. (2018) · Cancer · doi:10.1002/cncr.31629 · Cited by 486
George, S., Miao, D., Demetri, G. D., Adeegbe, D. O., Rodig, S. J., Shukla, S. A., Lipschitz, M., Amin‐Mansour, A., Raut, C. P., Carter, S. L., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.02.001 · Cited by 481
Nakanishi, J., Wada, Y., Matsumoto, K., Azuma, M., Kikuchi, K., & Ueda, S. (2007) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-006-0266-z · Cited by 473
Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma
Weber, J. S., O’Day, S., Urba, W., Powderly, J., Nichol, G., Yellin, M., Snively, J., & Hersh, E. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.1927 · Cited by 463
Nayak, L., Iwamoto, F. M., LaCasce, A., Mukundan, S., Roemer, M. G. M., Chapuy, B., Armand, P., Rodig, S. J., & Shipp, M. A. (2017) · Blood · doi:10.1182/blood-2017-01-764209 · Cited by 453
Pembrolizumab Cutaneous Adverse Events and Their Association With Disease Progression
Sanlorenzo, M., Vujic, I., Daud, A., Algazi, A., Gubens, M., Luna, S. A., Lin, K., Quaglino, P., Rappersberger, K., & Ortiz-Urda, S. (2015) · JAMA Dermatology · doi:10.1001/jamadermatol.2015.1916 · Cited by 449
Genomic correlates of response to immune checkpoint blockade
Keenan, T. E., Burke, K. P., & Van Allen, E. M. (2019) · Nature Medicine · doi:10.1038/s41591-019-0382-x · Cited by 448
PD‐1/PD‐L1 pathway: Basic biology and role in cancer immunotherapy
Salmaninejad, A., Valilou, S. F., Shabgah, A. G., Aslani, S., Alimardani, M., Pasdar, A., & Sahebkar, A. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28358 · Cited by 445
Blockade of CTLA-4 on CD4+CD25+ regulatory T cells abrogates their function in vivo
Read, S., Greenwald, R., Izcue, A., Robinson, N., Mandelbrot, D., Francisco, L., Sharpe, A. H., & Powrie, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.7.4376 · Cited by 434
Mechanisms of Resistance to PD-1 and PD-L1 Blockade
Nowicki, T. S., Hu‐Lieskovan, S., & Ribas, A. (2018) · The Cancer Journal · doi:10.1097/ppo.0000000000000303 · Cited by 408
Chambers, C. A., Sullivan, T. J., & Allison, J. P. (1997) · Immunity · doi:10.1016/s1074-7613(00)80406-9 · Cited by 406
PD-1 Blockade Expands Intratumoral Memory T Cells
Ribas, A., Shin, D. S., Zaretsky, J., Frederiksen, J., Cornish, A., Avramis, E., Seja, E., Kivork, C., Siebert, J., Kaplan-Lefko, P., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0210 · Cited by 405
Manipulation of T cell costimulatory and inhibitory signals for immunotherapy of prostate cancer
Kwon, E. D., Hurwitz, A. A., Foster, B. A., Madias, C. A., Feldhaus, A. L., Greenberg, N. M., Burg, M. B., & Allison, J. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8099 · Cited by 396
Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy
Mayoux, M., Roller, A., Pulko, V., Sammicheli, S., Chen, S., Sum, E., Jost, C., Fransen, M. F., Buser, R. B., Kowanetz, M., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.aav7431 · Cited by 394
Hurwitz, A. A., Yu, T. F.-Y., Leach, D. R., & Allison, J. P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.17.10067 · Cited by 385
Improved Survival with T Cell Clonotype Stability After Anti–CTLA-4 Treatment in Cancer Patients
Cha, E., Klinger, M., Hou, Y., Cummings, C., Ribas, A., Faham, M., & Fong, L. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008211 · Cited by 383
Gebhardt, C., Sevko, A., Jiang, H., Lichtenberger, R., Reith, M., Tarnanidis, K., Holland-Letz, T., Umansky, L., Beckhove, P., Sucker, A., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-0676 · Cited by 367
Interferon gamma in cancer immunotherapy
Ni, L., & Lu, J. (2018) · Cancer Medicine · doi:10.1002/cam4.1700 · Cited by 360
Kaufman, H. L., Russell, J. S., Hamid, O., Bhatia, S., Terheyden, P., D’Angelo, S. P., Shih, K. C., Lebbé, C., Milella, M., Brownell, I., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0310-x · Cited by 334
T cell–induced CSF1 promotes melanoma resistance to PD1 blockade
Neubert, N. J., Schmittnaegel, M., Bordry, N., Nassiri, S., Wald, N., Martignier, C., Tillé, L., Homicsko, K., Damsky, W., Maby-El Hajjami, H., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan3311 · Cited by 308
The CD28 and CTLA-4 Receptors Associate with the Serine/Threonine Phosphatase PP2A
Chuang, E., Fisher, T. S., Morgan, R. W., Robbins, M. D., Duerr, J. M., Vander Heiden, M. G., Gardner, J. P., Hambor, J. E., Neveu, M. J., & Thompson, C. B. (2000) · Immunity · doi:10.1016/s1074-7613(00)00031-5 · Cited by 303
Zheng, S. G., Wang, J. H., Stohl, W., Kim, K. S., Gray, J. D., & Horwitz, D. A. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.6.3321 · Cited by 297
Karachaliou, N., Gonzalez-Cao, M., Crespo, G., Drozdowskyj, A., Aldeguer, E., Gimenez-Capitan, A., Teixido, C., Molina-Vila, M. A., Viteri, S., De Los Llanos Gil, M., et al. (2018) · Therapeutic Advances in Medical Oncology · doi:10.1177/1758834017749748 · Cited by 285
Remark, R., Becker, C., Gomez, J. E., Damotte, D., Dieu‐Nosjean, M., Sautès‐Fridman, C., Fridman, W. H., Powell, C. A., Altorki, N. K., Mérad, M., et al. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201409-1671pp · Cited by 283
CD4+ regulatory T cells require CTLA-4 for the maintenance of systemic tolerance
Friedline, R. H., Brown, D. S., Nguyen, H., Kornfeld, H., Lee, J., Zhang, Y., Appleby, M. W., Der, S. D., Kang, J., & Chambers, C. A. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20081811 · Cited by 266
CD4+ T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy
Kagamu, H., Kitano, S., Yamaguchi, O., Yoshimura, K., Horimoto, K., Kitazawa, M., Fukui, K., Shiono, A., Mouri, A., Nishihara, F., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0574 · Cited by 256
Simeone, E., Gentilcore, G., Giannarelli, D., Grimaldi, A. M., Caracò, C., Curvietto, M., Esposito, A., Paone, M., Palla, M., Cavalcanti, E., et al. (2014) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-014-1545-8 · Cited by 253
Structural Analysis of CTLA-4 Function In Vivo
Masteller, E. L., Chuang, E., Mullen, A. C., Reiner, S. L., & Thompson, C. B. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.5319 · Cited by 252
Hopkins, A. C., Yarchoan, M., Durham, J. N., Yusko, E. C., Rytlewski, J. A., Robins, H. S., Laheru, D. A., Le, D. T., Lutz, E. R., & Jaffee, E. M. (2018) · JCI Insight · doi:10.1172/jci.insight.122092 · Cited by 233
Postow, M. A., Manuel, M., Wong, P., Yuan, J., Dong, Z., Liu, C., Perez, S., Tanneau, I., Noel, M., Courtier, A., et al. (2015) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-015-0070-4 · Cited by 232
Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease
Boyiadzis, M. M., Kirkwood, J. M., Marshall, J. L., Pritchard, C. C., Azad, N. S., & Gulley, J. L. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0342-x · Cited by 219
Sade-Feldman, M., Kanterman, J., Klieger, Y., Ish-Shalom, E., Olga, M., Saragovi, A., Shtainberg, H., Lotem, M., & Baniyash, M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-3104 · Cited by 201
Tinsley, N., Zhou, C., Tan, G., Rack, S., Lorigan, P., Blackhall, F., Krebs, M., Carter, L., Thistlethwaite, F., Graham, D., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2019-0160 · Cited by 201
Reversal of Autoimmune Toxicity and Loss of Tumor Response by Interleukin-17 Blockade
Esfahani, K., & Miller, W. H. (2017) · New England Journal of Medicine · doi:10.1056/nejmc1703047 · Cited by 200
Subrahmanyam, P. B., Dong, Z., Gusenleitner, D., Giobbie-Hurder, A., Severgnini, M., Zhou, J., Manos, M., Eastman, L. M., Maecker, H. T., & Hodi, F. S. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0328-8 · Cited by 190
Martens, A., Wistuba-Hamprecht, K., Yuan, J., Postow, M. A., Wong, P., Capone, M., Madonna, G., Khammari, A., Schilling, B., Sucker, A., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-0249 · Cited by 180
Bajwa, R., Cheema, A., Khan, T., Amirpour, A., Paul, A., Chaughtai, S., Patel, S., Patel, T., Bramson, J., Gupta, V., et al. (2019) · Journal of Clinical Medicine Research · doi:10.14740/jocmr3750 · Cited by 179
CTLA-4 trafficking and surface expression
Valk, E., Rudd, C. E., & Schneider, H. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.02.011 · Cited by 177
PD1/PDL1 inhibitors for the treatment of advanced urothelial bladder cancer
Stenehjem, D., Tran, D., Nkrumah, M., & Gupta, S. (2018) · OncoTargets and Therapy · doi:10.2147/ott.s135157 · Cited by 144
Zappasodi, R., Budhu, S., Hellmann, M. D., Postow, M. A., Senbabaoglu, Y., Manne, S., Gasmi, B., Liu, C., Zhong, H., Li, Y., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.05.009 · Cited by 142
de Coaña, Y. P., Wolodarski, M., Poschke, I., Yoshimoto, Y., Yang, Y., Nyström, M., Edbäck, U., Brage, S. E., Lundqvist, A., Masucci, G. V., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.15368 · Cited by 139
He, Y., Zhang, G., Wang, X., Zhang, H., Yuan, Y., Li, D., & Feng, Z. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.8.4919 · Cited by 125
De Angulo, G., Yuen, C., Palla, S. L., Anderson, P. M., & Zweidler‐McKay, P. A. (2008) · Cancer · doi:10.1002/cncr.23168 · Cited by 123
Chae, Y. K., Chiec, L., Mohindra, N., Gentzler, R., Patel, J., & Giles, F. (2017) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-016-1913-7 · Cited by 121
Regulation of Cytotoxic T Lymphocyte-Associated Molecule-4 by Src Kinases
Chuang, E., Lee, K.-M., Robbins, M. D., Duerr, J. M., Alegre, M.-L., Hambor, J. E., Neveu, M. J., Bluestone, J. A., & Thompson, C. B. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1270 · Cited by 119
Wistuba-Hamprecht, K., Martens, A., Heubach, F., Romano, E., Geukes Foppen, M., Yuan, J., Postow, M., Wong, P., Mallardo, D., Schilling, B., et al. (2017) · European Journal of Cancer · doi:10.1016/j.ejca.2016.12.011 · Cited by 108
Huang, L., Malu, S., McKenzie, J. A., Andrews, M. C., Talukder, A. H., Tieu, T., Karpinets, T., Haymaker, C., Forget, M.-A., Williams, L. J., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2483 · Cited by 102
CTLA-4 Ligation Suppresses CD28-induced NF-κB and AP-1 Activity in Mouse T Cell Blasts
Olsson, C., Riebeck, K., Dohlsten, M., & Michaëlsson, E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.20.14400 · Cited by 84
Valk, E., Leung, R., Kang, H., Kaneko, K., Rudd, C. E., & Schneider, H. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.024 · Cited by 78
Balatoni, T., Mohos, A., Papp, E., Sebestyén, T., Liszkay, G., Oláh, J., Varga, A., Lengyel, Z., Emri, G., Gaudi, I., et al. (2018) · Cancer Immunology, Immunotherapy · doi:10.1007/s00262-017-2072-1 · Cited by 76
Arakawa, A., Vollmer, S., Tietze, J., Galinski, A., Heppt, M. V., Bürdek, M., Berking, C., & Prinz, J. C. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01336 · Cited by 74
Marwitz, S., Scheufele, S., Perner, S., Reck, M., Ammerpohl, O., & Goldmann, T. (2017) · Clinical Epigenetics · doi:10.1186/s13148-017-0354-2 · Cited by 68
Woods, D. M., Ramakrishnan, R., Laino, A. S., Berglund, A., Walton, K., Betts, B. C., & Weber, J. S. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1100 · Cited by 66
Hurwitz, A. A., Townsend, S. E., Yu, T. F.-Y., Wallin, J. A., & Allison, J. P. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980703)77:1 · Cited by 47
CTLA-4 (CD152) inhibits T cell function by activating the ubiquitin ligase Itch
Hoff, H., Kolar, P., Ambach, A., Radbruch, A., & Brunner-Weinzierl, M. C. (2010) · Molecular Immunology · doi:10.1016/j.molimm.2010.03.017 · Cited by 39
Pirozyan, M. R., McGuire, H. M., Emran, A. A., Tseng, H.-Y., Tiffen, J. C., Lee, J. H., Carlino, M. S., Menzies, A. M., Long, G. V., Scolyer, R. A., et al. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00372 · Cited by 34
Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response
Felix, J., Lambert, J., Roelens, M., Maubec, E., Guermouche, H., Pages, C., Sidina, I., Cordeiro, D. J., Maki, G., Chasset, F., et al. (2016) · OncoImmunology · doi:10.1080/2162402x.2015.1136045 · Cited by 32
Grimaldi, A., Simeone, E., Festino, L., Giannarelli, D., Palla, M., Caracò, C., Curvietto, M., Esposito, A., Grimaldi, M., Mozzillo, N., et al. (2015) · Journal for ImmunoTherapy of Cancer · doi:10.1186/2051-1426-3-s2-p186 · Cited by 11
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- Yang YF, 1997, Cancer Res, 57, 4036
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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.
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