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Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-γ and IL-12
Open accessAbstract
&NA; Anti‐PD‐1 immune checkpoint blockers can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Here, we combined intravital real‐time imaging with single‐cell RNA sequencing analysis and mouse models to uncover anti‐PD‐1 pharmacodynamics directly within tumors. We showed that effective antitumor responses required a subset of tumor‐infiltrating dendritic cells (DCs), which produced interleukin 12 (IL‐12). These DCs did not bind anti‐PD‐1 but produced IL‐12 upon sensing interferon &ggr; (IFN‐&ggr;) that was released from neighboring T cells. In turn, DC‐derived IL‐12 stimulated antitumor T cell immunity. These findings suggest that full‐fledged activation of antitumor T cells by anti‐PD‐1 is not direct, but rather involves T cell:DC crosstalk and is licensed by IFN‐&ggr; and IL‐12. Furthermore, we found that activating the non‐canonical NF‐&kgr;B transcription factor pathway amplified IL‐12‐producing DCs and sensitized tumors to anti‐PD‐1 treatment, suggesting a therapeutic strategy to improve responses to checkpoint blockade. Graphical Abstract Figure. No caption available. HighlightsEffective anti‐PD‐1 anti‐tumor responses require IL‐12‐producing dendritic cellsAnti‐PD‐1 indirectly activates IL‐12 through IFN‐&ggr; produced from CD8+ T cellsAgonizing the non‐canonical NF‐&kgr;B pathway enhances dendritic cell IL‐12 productionCombining aPD‐1 with non‐canonical NF‐&kgr;B agonism enhances checkpoint immunotherapy &NA; Anti‐PD‐1 mAbs can induce sustained clinical responses in cancer but how they function in vivo remains incompletely understood. Garris et al. show that effective anti‐PD‐1 immunotherapy requires intratumoral dendritic cells (DCs) producing IL‐12. Anti‐PD‐1 indirectly activates DCs through IFN‐&ggr; released from drug‐activated T cells. Furthermore, agonizing the non‐canonical NF‐&kgr;B pathway activates DCs and enhances aPD‐1 therapy in an IL‐12‐dependent manner.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
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“Stimulated CD8+ T cells substantially increased IFN-γ production in the presence of IL-12 (Figure 4C)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we did not find evidence of IFN-γ or IL-12 induction by aPD-1 in the local draining lymph node (Figure S4A and B)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
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In the paper
“Flow cytometry analysis confirmed these cells to be MHC class II+ F4/80– (Figure S1D)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
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In the paper
“IL-12p40-eYFP+ cells displayed a branched morphology (mean circularity index: 0.54 ± 0.4), suggesting they were DCs.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Successful aPD-1 treatment triggers endogenous IFN-γ and IL-12 responses within tumors
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“parabiosis of tumor-bearing mice indicated that these cells could derive from a blood circulating precursor (Figure S1E).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that intratumoral IL-12 substantially expanded IFN-γ-eYFP+ cells (5.9 ± 0.7 fold increase by day four; Figure 4A).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“scRNAseq data indicated that aPD-1 treatment triggered the proliferation of tumor-infiltrating CD8+ T cells (Figure S4C).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and were unresponsive to aPD-1 treatment (Figure 3F)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IFN-γ sensing by DCs controls IL-12 production
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In the paper
“blocking lymphocyte recirculation through treatment with the trafficking inhibitor FTY 720 did not affect the antitumor response to aPD-1 treatment (Figure S4D and E).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we found that IL-12+ DCs expressed CD103 in lung tumor models (Figure S2D).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- It may state two separate claims as one. 32
- Probably not a substantial claim. 21
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Intravital imaging of the tumor microenvironment revealed a 6.0 ± 1.1 (mean ± SEM) fold expansion of IFN-γ- eYFP+ cells one day after a single aPD-1 injection; this increase was sustained for up to 3 days post treatment (Figure 1B and S1A).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Successful aPD-1 treatment triggers endogenous IFN-γ and IL-12 responses within tumors
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The ability for IL-12+ cells to accumulate within tumors was supported by the real-time imaging observation that these cells were motile one day after aPD-1 treatment (motility coefficient: ~10 µm2/min; Figure 1G-H and Supplemental Video 1) and much less so on day five (<1 µm2/min; Figure 1G-H and Supplemental Video 2).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Successful aPD-1 treatment triggers endogenous IFN-γ and IL-12 responses within tumors
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Both DC subsets were largely negative for the macrophage colony-stimulating factor receptor Csf1r (Figure 2C), although some DC2s expressed this receptor (Figure S2A), similarly to a subset of intratumoral DCs previously reported (Broz et al., 2014).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
What the sources say
- Not checked yetcites Broz et al., 2014 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Both DC1s and DC2s expressed the DC markers Batf3, Flt3, H2-Dmb2 and Zbtb46 (Meredith et al., 2012; Hildner et al., 2008;); DC1 expressed Fscn1 and Ly 75 (DEC-205) whereas DC2s expressed CD209a (DC- SIGN), Mgl2 (CD301b) and Cd24a (Figure 2B and Figure S2B).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
What the sources say
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and DC1s and DC2s expressed distinct chemokines and chemokine receptors (Figure 2E).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Decreased IL-12 production by DCs (Figure S3D) and decreased numbers of IL-12+ DCs (Figure S3E, F) both contributed to this reduction.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IFN-γ sensing by DCs controls IL-12 production
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Intravital imaging further revealed a 12.1 ± 3.7 fold increase of IL-12p40-eYFP+ cells on day one post treatment, which persisted for at least five days (Figure 1C and S1C).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Successful aPD-1 treatment triggers endogenous IFN-γ and IL-12 responses within tumors
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“DC1s had higher expression of the granulocyte/macrophage colony-stimulating factor receptor Csf2rb compared to DC2s, and neither DC1s nor DC2s expressed the granulocyte colony-stimulating factor receptor Csf3r (Figure 2C).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“in the experimental setups used in this study we found that CD8+ T cells and DCs are the primary producers of IFN-γ and IL-12, respectively”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“We confirmed that IL-12+ cells had more cell surface CD40 than their IL-12– counterparts (Figure S6A) and that IL-12+ DCs expressed more CD40 than tumor-associated macrophages (Figure S6B).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Activation of the non-canonical NFkB pathway amplifies IL-12-producing DCs
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“treatment with either agonistic aCD40 mAbs or AZD5582 provided antitumor effects in vivo (Figure 7B).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Amplification of IL-12+ DCs improves cancer immunotherapy in an IL-12-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that combining aPD-1 with aCD40 mAbs controlled B16F10 tumor growth (Figure S7E and F) and resulted in increased mouse survival (Figure 7D), when compared to aPD-1 or aCD40 monotherapies.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Amplification of IL-12+ DCs improves cancer immunotherapy in an IL-12-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“since IL-12+ DCs express the highest levels of CD28’s co-stimulatory ligands, CD80 and CD86”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“In total, 4095 cells (1154 untreated and 2941 aPD-1 treated cells) passed QC and were sequenced.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > METHOD DETAILS > Single Cell RNA Sequencing
Strength:plain· not yet calibratedn = 4,095Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“IFNG was not detectably increased in the post-treatment samples, which is expected from the timing of tissue collection and rapid on/off cycling of IFN-γ production by T cells (Slifka et al., 1999).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in cancer patients
What the sources say
- Not checked yetcites Slifka et al., 1999 source
Strength:plain· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that monotherapies incompletely controlled tumor growth, whereas the combination treatment produced a complete, durable response in most animals treated (Figure 7C and Figure S7B and C).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Amplification of IL-12+ DCs improves cancer immunotherapy in an IL-12-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“These findings indicate that aPD-1 delivery to tumors functionally impacts at least two non-overlapping cell populations, which respond differently to treatment: CD8+ T cells that activate the IFN- γ signaling pathway , and DC-like cells that turn on IL-12 production.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Successful aPD-1 treatment triggers endogenous IFN-γ and IL-12 responses within tumors
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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 discrepancy may be due to tissue location, as we found that IL-12+ DCs expressed CD103 in lung tumor models (Figure S2D).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > scRNAseq shows DC-restricted IL-12 production
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The requirement for both T cell co-stimulation and IL-12 to achieve maximal IFN-γ response likely reflected the need of CD28 to rescue exhausted CD8+ T cells, and possibly also the role of PD-1 in limiting CD28-mediated co-stimulation (Kamphorst et al., 2017; Hui et al., 2017).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IL-12 activates tumor-infiltrating lymphocyte effector functions in mice
What the sources say
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt 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
“Together, we find an indirect aPD-1 effect on DCs; this effect was mediated through IFN-γ and is critical for IL-12 induction and, consequently , treatment response.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > IFN-γ sensing by DCs controls IL-12 production
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Collectively , these data indicate that aPD-1 treatment induces IL-12 production by DCs, and that both DCs and IL-12 critically regulate aPD-1 treatment potency .”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > DCs and IL-12 are relevant to aPD-1 therapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“All biopsies were from University of California, San Francisco Medical Center-Mt. Zion, San Francisco, and Huntsman Cancer Institute, Salt Lake City , Utah, and were approved by each organization’s institutional review board.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“IL-12 production required DC sensing of IFN-γ , and, in turn, licensed effector T cell responses in both mice and cancer patients.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“targeted intratumoral delivery of IL-12 encoding plasmids is safe and has already demonstrated antitumor efficacy as monotherapy (Daud et al., 2008).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
- Not checked yetcites Daud et al., 2008 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“starting tumor volumes were normalized between treatment groups.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“We suggest further that responses to immunotherapy can be improved through rational drug combinations that accentuate the crosstalk between lymphoid and myeloid immune compartments.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✗ Checkable: fails✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may be too vague to check against evidence.
In the paper
“besides their critical role for priming T cells in lymph nodes (Martin-Fontecha et al., 2003)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
- Not checked yetcites Martin-Fontecha et al., 2003 source
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“IL-12 may be both a marker and functional feature of immunostimulatory tumor DCs, based on our findings that i) IL-12+ DCs share many features with cross-presenting DC1 cells, including expression of Batf3, Irf8, Flt3, and Ly 75 (DEC205), and ii) IL-12 is required for immunotherapy efficacy”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Caveats still exist with this imaging approach however as distribution and effector functions of antibodies may differ between species and antibody compositions.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✗ Based: failsProbably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The study was approved by the local Ethical Review Board (Ethikkommission Nordwestschweiz) and University Hospital Basel, Switzerland.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Taken together, these data linked the non-canonical NFkB pathway to antitumor intratumoral DCs and to aPD-1 treatment efficacy , and indicated that targeting non-canonical NFkB components can be therapeutic in cancer.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Amplification of IL-12+ DCs improves cancer immunotherapy in an IL-12-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Blood from mice was used to confirm lymphocyte trafficking defects.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > METHOD DETAILS > FTY 720 Treatments
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. The quote only partly states this claim.
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
“antitumor immune functions may not necessarily be cell type-dependent”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data indicate that DC targeting can augment immunotherapy efficacy and sensitize tumors to aPD-1 treatment in an IL-12-dependent manner.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Results > Amplification of IL-12+ DCs improves cancer immunotherapy in an IL-12-dependent manner
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All patients consented in writing to the analysis of their tumor samples.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedn = 6Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“under different experimental contexts it is possible that NK cells may also produce IFN-γ and macrophages may also produce IL-12.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“The findings presented here align with the notion that intratumoral DCs can exhibit key antitumor functions and promote aPD-1 immunotherapy.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Mouse tumors were allowed to grow to a maximum of 2 cm in diameter, or until tumor ulceration occurred. These were considered as endpoints for survival experiments in accordance with MGH IACUC regulations.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Treatments combining CD40 agonists with PD-1 pathway inhibitors (NCT03123783, NCT02376699), and cIAP inhibitors with aPD-L1 (NCT03270176), are currently in clinical trials.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
- Not checked yetcites NCT03123783
- Not checked yetcites NCT02376699
- Not checked yetcites NCT03270176
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“We suggest that both treatment strategies may rely upon the non-canonical NFkB pathway and DCs.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“We also showed that IL-12-producing DCs were enriched for non-canonical NFkB signaling pathway components, that the critical non-canonical NFkB kinase NIK was required for aPD-1 response, and that agonism of the non-canonical NFkB pathway in a therapeutic setting produced an IL-12-dependent antitumor response.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“prior evidence that cross- presenting tumor DCs have elevated IL-12 expression (Broz et al., 2014; Ruffell et al., 2014)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“the cDC1 subtype of DCs, which resembles the DC1 subtype presented here, is adept at cross- presenting antigens (Schlitzer and Ginhoux, 2014)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
- Not checked yetcites Schlitzer and Ginhoux, 2014
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“recent studies demonstrated that DCs can be found in tumors, where they recruit T cells and stimulate tumor-reactive T cell responses locally (Spranger et al., 2014; de Mingo Pulido et al., 2018)”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Real-time in vivo imaging allows one to identify not only primary targets of immunotherapeutics (drug pharmacokinetics) (Arlauckas et al., 2017) but also how the tumor microenvironment responds to treatment (drug pharmacody namics).”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
What the sources say
- Not checked yetcites Arlauckas et al., 2017 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“Principally , we identified that aPD-1 directly induced IFN-γ production by activated T cells, but indirectly induced IL-12 production by a subset of intratumoral DCs.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Experiments were approved by the MGH Institutional Animal Care and Use Committee (IACUC) and were performed in accordance with MGH IACUC regulations.”
§ Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-γ and IL-12 > STAR METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
B cell depletion did not affect anti-CD40 therapy in this experimental model.
“We found that B cell depletion had no effect on aCD40 therapy , suggesting that B cells are not necessary for aCD40 treatment in this experimental model (data not shown).”
The paper relies on this without support.
The MC38 tumor model responds to anti-PD-1 treatment.
“Here, we initially used the MC38 mouse tumor model because it is sensitive to aPD-1 treatment and thus is relevant to define mechanisms dictating treatment success.”
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In the citing 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).”
From Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance (2021) · cites this paper as [91]
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Peña-Romero, A. C., & Orenes‐Piñero, E. (2022) · Cancers · doi:10.3390/cancers14071681 · Cited by 271
IFN-γ: A cytokine at the right time, is in the right place
Burke, J. D., & Young, H. A. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.05.002 · Cited by 272
Zhang, Z., Tang, H., Chen, P., Xie, H., & Tao, Y. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0074-5 · Cited by 263
“DC-derived IL-12 enhances the capacity of Teff cells to eliminate malignant cells.(448) Anti-CTLA-4 mAb is potentially endowed with different properties.”
BackgroundRadiation-induced tumor immune microenvironments and potential targets for combination therapy
Guo, S., Yao, Y., Tang, Y., Xin, Z., Wu, D., Ni, C., Huang, J., Wei, Q., & Zhang, T. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01462-z · Cited by 290
Tumor-infiltrating dendritic cell states are conserved across solid human cancers
Gerhard, G. M., Bill, R., Messemaker, M., Klein, A. M., & Pittet, M. J. (2020) · The Journal of Experimental Medicine · doi:10.1084/jem.20200264 · Cited by 254
“T cells (Garris et al., 2018) or NK cells (Mittal et al.”
BackgroundInfluentialSelf-citationInterferon-γ induces tumor resistance to anti-PD-1 immunotherapy by promoting YAP phase separation
Yu, M., Peng, Z., Qin, M., Liu, Y., Wang, J., Zhang, C., Lin, J., Dong, T., Wang, L., Li, S., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.01.010 · Cited by 250
Menares, E., Gálvez‐Cancino, F., Morgado-Cáceres, P., Ghorani, E., López, E., Díaz, X., Saavedra-Almarza, J., Figueroa, D. A., Roa, E., Quezada, S. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12319-x · Cited by 255
Gao, S., Yang, X., Xu, J., Qiu, N., & Zhai, G. (2021) · ACS Nano · doi:10.1021/acsnano.1c02103 · Cited by 242
Mansurov, A., Ishihara, J., Hosseinchi, P., Potin, L., Marchell, T. M., Ishihara, A., Williford, J., Alpar, A. T., Raczy, M. M., Gray, L. T., et al. (2020) · Nature Biomedical Engineering · doi:10.1038/s41551-020-0549-2 · Cited by 230
Lecoultre, M., Dutoit, V., & Walker, P. R. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001408 · Cited by 223
The landscape of bispecific T cell engager in cancer treatment
Zhou, S., Liu, M., Ren, F., Meng, X., & Yu, J. (2021) · Biomarker Research · doi:10.1186/s40364-021-00294-9 · Cited by 240
“A major reason for this is the lack of a sufficient number of tumor-infiltrating immune cells (TILs), primarily T cells, in the tumor site, which is referred to as exhibiting cold phenotype [9].”
BackgroundIntratumoral IL12 mRNA Therapy Promotes TH1 Transformation of the Tumor Microenvironment
Hewitt, S. L., Bailey, D., Zielinski, J. F., Apte, A., Musenge, F. M., Karp, R., Burke, S., Garçon, F., Mishra, A., Gurumurthy, S., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-0472 · Cited by 231
“IL12 release from tumoral DC was reported recently to be required for effective anti-PD-1 immunotherapy in a PD-1 blockade– sensitive MC38 model (42).”
BackgroundPelly, V. S., Moeini, A., Roelofsen, L. M., Bonavita, E., Bell, C. R., Hutton, C., Blanco‐Gómez, A., Banyard, A., Bromley, C. P., Flanagan, E., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-1815 · Cited by 230
“S4C), in line with a reported peak in IFN-γ production two days following αPD-1 treatment (36).”
BackgroundResultWang, G., Kang, X., Chen, K. S., Jehng, T., Jones, L. E., Chen, J., Huang, X. F., & Chen, S. (2020) · Nature Communications · doi:10.1038/s41467-020-15229-5 · Cited by 232
Exploiting innate immunity for cancer immunotherapy
Yi, M., Li, T., Niu, M., Mei, Q., Zhao, B., Chu, Q., Dai, Z., & Wu, K. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01885-w · Cited by 250
Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity
Ma, L., Hostetler, A., Morgan, D. M., Maiorino, L., Sulkaj, I., Whittaker, C. A., Neeser, A., Pires, I. S., Yousefpour, P., Gregory, J. R., et al. (2023) · Cell · doi:10.1016/j.cell.2023.06.002 · Cited by 232
Boulch, M., Cazaux, M., Loe-Mie, Y., Thibaut, R., Corre, B., Lemaı̂tre, F., Grandjean, C. L., Garcia, Z., & Bousso, P. (2021) · Science Immunology · doi:10.1126/sciimmunol.abd4344 · Cited by 226
Stump, C. T., & Dougan, S. K. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.11.011 · Cited by 233
Advancing to the era of cancer immunotherapy
Wang, Y., Wang, M., Wu, H., & Xu, R. (2021) · 癌症：英文版 · doi:10.1002/cac2.12178 · Cited by 221
Meiser, P., Knolle, M. A., Hirschberger, A., de Almeida, G. P., Bayerl, F., Lacher, S. B., Pedde, A., Flommersfeld, S., Hönninger, J., Stark, L., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.06.008 · Cited by 208
Obradovic, A., Graves, D. K., Korrer, M. J., Wang, Y., Roy, S., Naveed, A., Xu, Y., Luginbuhl, A., Curry, J., Gibson, M. K., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-3570 · Cited by 215
Bayerl, F., Meiser, P., Donakonda, S., Hirschberger, A., Lacher, S. B., Pedde, A., Hermann, C. D., Elewaut, A., Knolle, M. A., Ramsauer, L., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.05.011 · Cited by 218
Self-citationImmune checkpoint blockade and CAR-T cell therapy in hematologic malignancies
Wang, H., Kaur, G., Sankin, A. I., Chen, F., Guan, F., & Zang, X. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0746-1 · Cited by 210
Recent Advances in Engineered Materials for Immunotherapy‐Involved Combination Cancer Therapy
Liang, J., Luo, G., Chen, W., & Zhang, X. (2021) · Advanced Materials · doi:10.1002/adma.202007630 · Cited by 207
Cohen, M., Giladi, A., Barboy, O., Hamon, P., Li, B., Zada, M., Gurevich‐Shapiro, A., Beccaría, C. G., David, E., Maier, B. B., et al. (2022) · Nature Cancer · doi:10.1038/s43018-022-00338-5 · Cited by 204
“We analyzed 25 (10) patient samples that contained TCR-seq data for at least seven annotated T-cell subsets and considered a cell to belong to a clone if it shared a TCR sequence with at least one other T cell from the same patient.”
Dendritic cell derived exosomes loaded neoantigens for personalized cancer immunotherapies
Li, J., Li, J., Peng, Y., Du, Y., Yang, Z., & Qi, X. (2023) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.11.053 · Cited by 201
Haas, L., Elewaut, A., Gerard, C. L., Umkehrer, C., Leiendecker, L., Pedersen, M., Kręcioch, I., Hoffmann, D., Novatchkova, M., Kuttke, M., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00221-9 · Cited by 196
Chen, Y., Du, M., Yuan, Z., Chen, Z., & Yan, F. (2022) · Nature Communications · doi:10.1038/s41467-022-31932-x · Cited by 197
The tumor microenvironment’s role in the response to immune checkpoint blockade
Aliazis, K., Christofides, A., Shah, R., Yeo, Y. Y., Jiang, S., Charest, A., & Boussiotis, V. A. (2025) · Nature Cancer · doi:10.1038/s43018-025-00986-3 · Cited by 208
“PD-1 blockade also induced IFNγ production by intratumoral CD8 + T cells, which, in turn, stimulated IL-12 production by cDC1 cells, leading to CD8 + T cell activation and tumor eradication 82 , further supporting the direct role of DCs in ICB responses.”
Metabolic programming in dendritic cells tailors immune responses and homeostasis
Møller, S. H., Wang, L., & Ho, P. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00753-1 · Cited by 189
Dendritic cell maturation in cancer
Moon, C. Y., Belabed, M., Park, M. D., Mattiuz, R., Puleston, D. J., & Mérad, M. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00787-3 · Cited by 189
“…enhancing ncNF-κB signalling through modulation of its negative regulators (for example, via SMAC mimetics ) has been shown to improve responsiveness to ICB treatment across multiple preclinical cancer models 238 and further underscoring the therapeutic potential of targeting this pathway 192 .”
Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade
Shergold, A. L., Millar, R., & Nibbs, R. J. B. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104258 · Cited by 176
PPARα Inhibition Overcomes Tumor-Derived Exosomal Lipid-Induced Dendritic Cell Dysfunction
Yin, X., Zeng, W., Wu, B., Wang, L., Wang, Z., Tian, H., Wang, L., Jiang, Y., Clay, R., Wei, X., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108278 · Cited by 175
“, 2011), as well as enhance the efficiency of checkpoint therapy (Garris et al., 2018).”
BackgroundNanomedicine‐Based Immunotherapy for the Treatment of Cancer Metastasis
Zhang, P., Zhai, Y., Cai, Y., Zhao, Y., & Li, Y. (2019) · Advanced Materials · doi:10.1002/adma.201904156 · Cited by 170
Li, Z., Wang, Y., Shen, Y., Qian, C., Oupický, D., & Sun, M. (2020) · Science Advances · doi:10.1126/sciadv.aaz9240 · Cited by 173
“Therefore, successful anti– PD-1/PD-L1 immunotherapy requires a close interaction between effector T cells and DCs, which can turn T cells soldiers into elite troops and provide enough information about the enemy ( 34 ).”
PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment
Gao, J., Xiong, A., Liu, J., Li, X., Wang, J., Zhang, L., Liu, Y., Xiong, Y., Li, G., & He, X. (2024) · Cancer Gene Therapy · doi:10.1038/s41417-024-00765-9 · Cited by 188
“Effective anti-tumor responses require a subset of tumor-in fi ltrating DCs, and T-cell-DC crosstalk involving the cytokines IFN-γ , which potentiate CD8 + T-cell-mediated tumor destruction [112].”
BackgroundHigh-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model
Luchtel, R. A., Bhagat, T. D., Pradhan, K., Jacobs, W. R., Levine, M., Verma, A. K., & Shenoy, N. K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1908158117 · Cited by 171
“Cross-talk between T cells and dendritic cells involving IL-12 has been recently shown to be crucial for successful antiPD1 therapy (35).”
Immunotherapy in hematologic malignancies: achievements, challenges and future prospects
Tang, L., Huang, Z., Mei, H., & Hu, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01521-5 · Cited by 181
Targeting NF-κB-Inducing Kinase (NIK) in Immunity, Inflammation, and Cancer
Pflug, K. M., & Sitcheran, R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228470 · Cited by 163
“This study further showed that the use of a cIAP antagonist on murine tumors increased invading dendritic cells and that chimera mice with NIK-deficient bone marrow had poor response to aPD-1 treatment [86].”
Thibaut, R., Bost, P., Milo, I., Cazaux, M., Lemaı̂tre, F., Garcia, Z., Amit, I., Bréart, B., Cornuot, C., Schwikowski, B., et al. (2020) · Nature Cancer · doi:10.1038/s43018-020-0038-2 · Cited by 163
Zagorulya, M., Yim, L., Morgan, D. M., Edwards, A. W., Torres-Mejia, E., Momin, N., McCreery, C. V., Zamora, I., Horton, B. L., Fox, J. G., et al. (2023) · Immunity · doi:10.1016/j.immuni.2023.01.010 · Cited by 160
Cancer cells impair monocyte-mediated T cell stimulation to evade immunity
Elewaut, A., Estivill, G., Bayerl, F., Castillon, L., Novatchkova, M., Pottendorfer, E., Hoffmann-Haas, L., Schönlein, M., Nguyễn, T. C. B., Lauss, M., et al. (2024) · Nature · doi:10.1038/s41586-024-08257-4 · Cited by 167
The role of dendritic cells in cancer
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KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance
Zavitsanou, A., Pillai, R., Yuan, H., Wu, W., Bartnicki, E., Karakousi, T. R., Rajalingam, S., Herrera, A. M., Karatza, A., Rashidfarrokhi, A., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.113295 · Cited by 157
“16,19,20,54,55 Keap1 -mutant tumors had higher numbers of CD8 exhausted T cells.”
BackgroundSufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity
Morrison, A. H., Diamond, M. S., Hay, C., Byrne, K. T., & Vonderheide, R. H. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1918971117 · Cited by 154
“Given the alterations within the effector and suppressive T cell subsets in the TME after αCD40 treatment, we next investigated if the posttreatment T cell population was more functional.”
BackgroundInfluentialPhase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma
Algazi, A. P., Twitty, C., Tsai, K. K., Le, M. H., Pierce, R. H., Browning, E., Hermiz, R., Canton, D. A., Bannavong, D., Oglesby, A., et al. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-2217 · Cited by 154
Self-citationIntratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells
Etxeberría, I., Bolaños, E., Quetglas, J. I., Gros, A., Villanueva, A., Palomero, J., Sánchez-Paulete, A. R., Piulats, J. M., Matías‐Guiu, X., Olivera, I., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.10.006 · Cited by 146
PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells
Balança, C.-C., Salvioni, A., Scarlata, C., Michelas, M., Gomez‐Roca, C., Gomez‐Roca, C., Sarradin, V., Tosolini, M., Valle, C., Pont, F., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.142513 · Cited by 166
“This is in agreement with the requirement for a DC and CD8 T cell crosstalk and IL-12 and IFN-γ secretion for responsiveness to immunotherapy (28).”
Dendritic Cells and Cancer: From Biology to Therapeutic Intervention
Wylie, B., Macri, C., Mintern, J. D., & Waithman, J. C. (2019) · Cancers · doi:10.3390/cancers11040521 · Cited by 149
Lactate oxidase nanocapsules boost T cell immunity and efficacy of cancer immunotherapy
Cao, Z., Xu, D., Harding, J., Chen, W., Liu, X., Wang, Z., Wang, L., Qi, T., Chen, S., Guo, X., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.add2712 · Cited by 145
“Immunotherapeutics, such as immune checkpoint blockade therapies ( 3 ), adoptive cell therapies ( 4 ), and cancer vaccines ( 5 ), have been integrated into standard-of-care regimens for cancers, including advanced melanoma ( 6 ), lymphoma ( 6 ), non – small cell lung cancer ( 7 ), and prostate…”
BackgroundWang, M., Zhai, X., Li, J., Guan, J., Xu, S., Li, Y., & Zhu, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.670391 · Cited by 143
“Moreover, IFN-g released by T cells stimulates neighboring dendritic cells (DCs) to produce IL-12, which in turn promotes the production of IFN-g and forms a positive feedback loop (91).”
BackgroundType I and II Interferons in the Anti-Tumor Immune Response
Fenton, S. E., Saleiro, D., & Platanias, L. C. (2021) · Cancers · doi:10.3390/cancers13051037 · Cited by 143
Dendritic Cells, the T-cell-inflamed Tumor Microenvironment, and Immunotherapy Treatment Response
Garris, C., & Luke, J. J. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1321 · Cited by 146
“Supplying exogenous IL12 intratumorally in combinationwith a T-cell agonizing CD137 antibody results in durable tumor rejection inMC38 murine models, however this effect is lost in Batf3 knockout mice (58).”
BackgroundInfluentialSelf-citationOba, T., Long, M. D., Keler, T., Marsh, H. C., Minderman, H., Abrams, S. I., Liu, S., & Ito, F. (2020) · Nature Communications · doi:10.1038/s41467-020-19192-z · Cited by 140
The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy
Cueto, F. J., & Sancho, D. (2021) · Cancers · doi:10.3390/cancers13071525 · Cited by 137
“IL12 is necessary for immune checkpoint therapy [85], but not sufficient to restore responsiveness to immune checkpoint therapy in cDC1-deficient mice [71].”
Background
Metadata
- Authors
- Garris, C. S., Arlauckas, S. P., Kohler, R. H., Trefny, M. P., Garren, S., Piot, C., Engblom, C., Pfirschke, C., Siwicki, M., Gungabeesoon, J., Freeman, G. J., Warren, S. E., Ong, S., Browning, E., Twitty, C. G., Pierce, R. H., Le, M. H., Algazi, A. P., Daud, A. I., Pai, S. I., Zippelius, A., Weissleder, R., & Pittet, M. J.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- University Hospital of Basel (CH)
- Nanostring Technologies (United States) (US)
- University of California, San Francisco (US)
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-12
- Volume
- 49
- Issue
- 6
- Pages
- 1148-1161.e7
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC6301092
- OpenAlex
- W2904099327
- Semantic Scholar
- 1209b0cd82a4fa3c176fbcbc8f01817d21cdace6
- Cited by
- 966
- References
- 62
- Citations by year
- 2026: 101 · 2025: 118 · 2024: 130 · 2023: 138 · 2022: 146 · 2021: 150 · 2020: 124 · 2019: 57 · 2018: 1
- FWCI
- 30.99
- Type
- journal article
- Language
- en
- Update notices
- erratum (2022-09-13)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Samana Cay MGH Research Scholar Fund
- Robert Wenner Award from the Swiss Cancer League
- NIH (R01-AI084880, R01-CA218579, R01-AI123349, R01-CA206890, R33-CA202064, U01CA206997, P01 AI056299, P50CA101942, F31-CA196035, T32-CA79443)
- Swiss National Cancer Foundation (320030_162575)
- MGH ECOR Tosteson Postdoctoral Fellowship
- 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
- anti-PD-1 therapy, immune checkpoint blockade, tumor-infiltrating dendritic cells, IL-12, interferon-gamma, T cell-mediated antitumor immunity, NF-κB signaling, intravital imaging, single-cell RNA sequencing, pharmacodynamics, cancer immunotherapy
- MeSH terms
- Adult, Aged, Aged, 80 and over, Animals, Antibodies, Monoclonal, Dendritic Cells, Female, Humans, Immunotherapy, Interferon-gamma, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Neoplasms, T-Lymphocytes, Signal Transduction, NF-kappa B, Interleukin-12, Programmed Cell Death 1 Receptor
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