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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.”
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?
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]
Citations
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PD-1 and Its Ligands in Tolerance and Immunity
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“These inhibitory pathways are important because they protect the host from uncontrolled immune activation (Keir et al., 2008) but they can also be co-opted by tumors, which make them resist immune attack (Wherry, 2011).”
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Molecular and genetic properties of tumors associated with local immune cytolytic activity
Rooney, M. S., Shukla, S. A., Wu, C. J., Getz, G., & Hacohen, N. (2015) · Cell · doi:10.1016/j.cell.2014.12.033 · Cited by 3,825 · cited 2×
“Comparison of pre- and post-treatment samples revealed that IL-12 delivery enhanced expression of core cytolytic genes (Rooney et al., 2015) within tumors (Figures 5A and 5B).”
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Items 501–600 of 970
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Reversing immune evasion using a DNA nano-orchestrator for pancreatic cancer immunotherapy
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Pharmacological Polarization of Tumor‐Associated Macrophages Toward a CXCL9 Antitumor Phenotype
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BackgroundLocal CpG-Stat3 siRNA treatment improves antitumor effects of immune checkpoint inhibitors
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Self-citationAdvances and perspectives of dendritic cell-based active immunotherapies in follicular lymphoma
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Self-citationTNIK Inhibition Has Dual Synergistic Effects on Tumor and Associated Immune Cells
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Self-citationDendritic cells control tertiary lymphoid structure development and maintenance in cancer
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An IFNγ/STAT1/JMJD3 Axis Induces ZEB1 Expression and Promotes Aggressiveness in Lung Adenocarcinoma
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“Garris and colleagues have demonstrated that effective anti-PD-1 cancer immunotherapy requires T-cell–dendritic cell crosstalk and involves the cytokines IFNg and IL12 (3).”
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Tumor-Reactive CD8+ T Cells Enter a TCF1+PD-1− Dysfunctional State
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Immunological Effects of Proton Radiotherapy: New Opportunities and Challenges in Cancer Therapy
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“DCs secrete IL ‐ 12 in response to IFN ‐ γ produced by activated CD8 + T cells through an atypical NF ‐ κ B ‐ dependent mechanism [34].”
Pilard, C., Roncarati, P., Ancion, M., Luyckx, M., Renard, M., Reynders, C., Lerho, T., Poulain, F., Bruyère, D., Lebeau, A., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010753 · Cited by 16
TPPP3 Associated with Prognosis and Immune Infiltrates in Head and Neck Squamous Carcinoma
Yang, Z., Li, X., Li, J., Su, Q., Qiu, Y., Zhang, Z., Zhang, L., & Mo, W. (2020) · BioMed Research International · doi:10.1155/2020/3962146 · Cited by 13
Pipperger, L., Riepler, L., Kimpel, J., Siller, A., Stoitzner, P., Bánki, Z., & von Laer, D. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1959140 · Cited by 13
Ultra‐fast Cycling for Multiplexed Cellular Fluorescence Imaging
Ko, J., Oh, J., Ahmed, M. S., Carlson, J., & Weissleder, R. (2020) · Angewandte Chemie · doi:10.1002/ange.201915153 · Cited by 13
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“HOXC6 facilitated proliferation and metastasis through the dickkopf-1 (DKK1)/Wnt/β-catenin axis in right-sided colon cancer (Qi et al., 2021; Garris et al., 2018).”
BackgroundMetformin keeps CD8+ T cells active and moving in NASH-HCC immunotherapy
Lujambio, A., & Sarobe, P. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.05.038 · Cited by 12
Zhang, P., Pan, J., Lin, S., Peng, B., Zhang, J., Zhang, J., Xu, L., Lai, Y. L., Yu, H., & Xu, Z. (2025) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2025.115620 · Cited by 13
Zhang, Y., & Liu, Z. (2025) · Advanced Science · doi:10.1002/advs.202508692 · Cited by 13
Dendritic cells: the central partner for cancer immunity
Laoubi, L., Gobbini, É., Duplouye, P., Hubert, M., Caux, C., Bendriss‐Vermare, N., Valladeau‐Guilemond, J., & Voissière, A. (2025) · OncoImmunology · doi:10.1080/2162402x.2025.2571773 · Cited by 12
Zheng, X., Zhu, J., Zheng, C., Tan, Z., Ji, Z., Jin, T., Zhao, Y., Ji, Z., & Hu, Y. (2023) · AAPS PharmSciTech · doi:10.1208/s12249-022-02473-9 · Cited by 12
“Both cytokines play an important role in immune activation [24].”
BackgroundGuo, Y., Shen, R., Yang, K., Wang, Y., Song, H., Liu, X., Cheng, X., Wu, R., Song, Y., & Wang, D. (2023) · Cell Death Discovery · doi:10.1038/s41420-023-01500-3 · Cited by 12
“NF-κB is another important regulator of gal-3 contributed to tumor growth and metastasis [20].”
BackgroundApplications of Intravital Imaging in Cancer Immunotherapy
Deng, D., Hao, T., Lu, L., Yang, M., Zeng, Z., Lovell, J. F., Liu, Y., & Jin, H. (2024) · Bioengineering · doi:10.3390/bioengineering11030264 · Cited by 13
“Garris CS et al. also found that tumor-infiltrating DCs, a class of immune cells that do not respond to PD-1 antibodies, could promote the therapeutic effects of ICIs by responding to the IFN-γ signals released by neighboring T cells and releasing cytokines such as IL-12 (Figure 2C) [106].”
Interleukins and interferons in mesenchymal stromal stem cell-based gene therapy of cancer
Švajger, U., & Kamenšek, U. (2024) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2024.03.002 · Cited by 12
Development of Cell Technologies Based on Dendritic Cells for Immunotherapy of Oncological Diseases
Васильевич, К. В., Alshevskaya, A., & Sennikov, S. V. (2024) · Biomedicines · doi:10.3390/biomedicines12030699 · Cited by 13
“…the active production of the cytokines CXCL9/CXCL10 and IL-12, which leads to activation and stimulation of infiltration of CD8+ T cells in tumors [51]. cDC1s are thought to be specialized not only for priming CD8+ T cells, but also for priming CD4+ T cells, which has a synergistic effect in…”
BackgroundKu, K. B., Kim, C. W., Kim, Y., Kang, B. H., La, J., Kang, I., Park, W. H., Ahn, S., Lee, S. K., & Lee, H. K. (2024) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-009449 · Cited by 12
“33 These findings suggest that Fcgr2b −/− CD8 T cell-derived Ttsms represent the most potential subsets for the efficacy of anti- PD-1 therapy.”
BackgroundOh, J., Hoelzl, J., Carlson, J. C. T., Bill, R., Peterson, H. M., Faquin, W., Pittet, M., Pai, S. I., & Weissleder, R. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102100 · Cited by 14
“55 In turn, IL-12 stimulates anti-tumor CD8 + T cells 55 or NK cells, 56 indicating that CCR7 + DCscan license full-fledged anti-tumor immunity through a molecular crosstalk involving IFN-γ and IL-12.”
Self-citationPiot, C., da Costa, M. P., Biram, A., Minutti, C. M., Lim, K. H. J., Green, M. J., Mikolajczak, A., Jenkins, R. P., Meader, L., Buck, M. D., et al. (2025) · European Journal of Immunology · doi:10.1002/eji.70011 · Cited by 11
Self-citationPotential and unsolved problems of anti-PD-1/PD-L1 therapy combined with radiotherapy
Cao, Y., Li, W., Wang, Z., & Pang, H. (2020) · Tumori Journal · doi:10.1177/0300891620940382 · Cited by 12
Research advances of secretory proteins in malignant tumors
Zhang, N., Hao, J., Cai, Y., & Wang, M. (2021) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2021.01.12 · Cited by 12
Xia, Z., Wu, J., Yao, W., Meng, Y., Jian, W., Wang, T., Xue, W., Yu, Y., Cai, L., Wang, X., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-15206-6 · Cited by 14
Recent Advances in the Management of Anal Cancer
Upadhyay, L., Hartzell, M., Parikh, A. R., Strickland, M. R., Klempner, S. J., & Malla, M. (2023) · Healthcare · doi:10.3390/healthcare11233010 · Cited by 12
Wang, J., Chang, C., Yang, X. F., Zhou, F., Liu, J., Zhu, S., Yu, X., Liu, C., O’Sullivan, T. E., Xie, P., et al. (2022) · Blood · doi:10.1182/blood.2022015677 · Cited by 13
Flores‐Santibáñez, F., Rennen, S., Fernández, D., Nolf, C. D., Velde, E. V. D., González, S. G., Fuentes, C., Moreno, C., Figueroa, D. A., Lladser, Á., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1209588 · Cited by 11
Gorodilova, A. V., Kitaeva, K. V., Filin, I. Y., Mayasin, Y. P., Kharisova, C. B., Issa, S. S., Solovyeva, V. V., & Rizvanov, A. A. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45100509 · Cited by 12
“[27]. cDC1s are also specialized in activating CD8 + naive T-cells through cross-presentation via MHC I molecules, playing a crucial role in anti-tumor and antiviral immune responses The presence of Toll-like receptor 3 (TLR3), an endosomal protein, is characteristic of cDC1s, and it is necessary…”
BackgroundBakhshi, P., Nourizadeh, M., Sharifi, L., Farajollahi, M. M., & Mohsenzadegan, M. (2023) · Cancer Cell International · doi:10.1186/s12935-023-03108-0 · Cited by 11
“Evaluating cytokine-12 has the potential to provide valuable insight into DC-T cell crosstalk [32].”
BackgroundDeng, Z., Liu, J., Yu, Y. V., & Jin, Y. N. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1451103 · Cited by 13
Wang, S., Meng, L., Xu, N., Chen, H., Xiao, Z., Lu, D., Fan, X., Xia, L., Chen, J., Zheng, S., et al. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01215-0 · Cited by 12
“Effective ICB therapy relies on the presence of intratumoral IL-12-producing DCs to optimize antitumor CD8 + T-cell responses [6].”
The role of sialoglycans in modulating dendritic cell function and tumour immunity
Silva, Z., Soares, C. O., Barbosa, M., Palma, A. S., Marcelo, F., & Videira, P. A. (2024) · Seminars in Immunology · doi:10.1016/j.smim.2024.101900 · Cited by 11
Kaiser, Y., Garris, C., Marinari, E., Kim, H. S., Oh, J., Pédard, M., Halabi, E. A., Choi, M., Parvanian, S., Köhler, R. H., et al. (2025) · Nature Biomedical Engineering · doi:10.1038/s41551-025-01533-2 · Cited by 12
Self-citationImai, J., Ohashi, S., & Sakai, T. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics12020153 · Cited by 12
“However, CP by DCs is essential for the successful outcome of these methods [25].”
BackgroundCCR5 is a prognostic biomarker and an immune regulator for triple negative breast cancer
Wang, X., Han, Y. K., Peng, J., & He, J. (2021) · Aging · doi:10.18632/aging.203654 · Cited by 11
“It is reported that effective anti-PD1 therapy requires the crosstalk between T cells and intratumoral dendritic cells (DCs) [18].”
BackgroundChen, Q., Du, X., Hu, S., & Huang, Q. (2022) · BioMed Research International · doi:10.1155/2022/5092505 · Cited by 11
“According to previous study, a total of 42 ICGs were selected for further analysis [37 – 45].”
West, E. J., Scott, K. J., Tidswell, E. L., Bendjama, K., Stojkowitz, N., Lusky, M., Kurzawa, M., Prasad, R. K., Toogood, G. J., Ralph, C., et al. (2022) · Cancers · doi:10.3390/cancers14092181 · Cited by 11
“Accordingly, a similar differential response was observed in the induction of IFN-stimulated inflammatory cytokines at D2: the T cell stimulants IL-2 receptor alpha chain (IL-2Rα) and IL-12p40 [37,38], the NK cell-stimulating cytokine IL-18 [39] and the pro-apoptotic cytokine TNF-related apoptosis-inducing ligand (TRA…”
ResultDendritic cells metabolism: a strategic path to improve antitumoral DC vaccination
Currivan, E., Finlay, D. K., & Moreira, D. (2022) · Clinical & Experimental Immunology · doi:10.1093/cei/uxac048 · Cited by 11
Burandt, E., Blessin, N. C., Rolschewski, A.-C., Lutz, F., Mandelkow, T., Yang, C. H., Bady, E., Reiswich, V., Simon, R., Sauter, G., et al. (2022) · Cancers · doi:10.3390/cancers14174246 · Cited by 11
“, metabolic barriers [51], TGF-ß [52], CD47-SIRPalpha signaling axis [53], immune checkpoint expression [23]) along the invasive margin were found preventing TILs from entering the tumor center in the immune excluded phenotype.”
BackgroundYeo, B. S. Y., Song, H. J. J. M. D., Soong, Y. L., Chua, M. L. K., Ang, M., Lim, W., See, A., & Lim, C. M. (2022) · Oral Oncology · doi:10.1016/j.oraloncology.2022.106242 · Cited by 12
Cancer Cell Resistance to IFNγ Can Occur via Enhanced Double-Strand Break Repair Pathway Activity
Han, T., Wang, X., Shi, S., Zhang, W., Wang, J., Wu, Q., Li, Z., Fu, J., Zheng, R., Zhang, J., et al. (2023) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-22-0056 · Cited by 11
Harnessing dendritic cell diversity in cancer immunotherapy
Park, H., Ashayeripanah, M., & Chopin, M. (2023) · Current Opinion in Immunology · doi:10.1016/j.coi.2023.102341 · Cited by 11
Autoimmune Bell’s Palsy Following Immunotherapy For Metastatic Melanoma: A Report of 2 Cases
Zieman, D. P., & Frankel, A. E. (2019) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000291 · Cited by 11
Laser‐assisted epicutaneous immunization to target human skin dendritic cells
Tripp, C. H., Voit, H., An, A., Seidl‐Philipp, M., Krapf, J., Sigl, S., Romani, N., Frari, B. D., & Stoitzner, P. (2021) · Experimental Dermatology · doi:10.1111/exd.14346 · Cited by 11
Archetypes of checkpoint-responsive immunity
Im, K. W., Combes, A. J., Spitzer, M. H., Satpathy, A. T., & Krummel, M. F. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.09.007 · Cited by 13
“…cDC1s in mouse tumors (characterized by the expression of the CD103 integrin) are unique in expressing high amounts of the stimulatory cytokine IL-12 [35 – 37], as well as in their capacity to cross-present tumor antigens on MHC I by maintaining ingested proteins in a neutral pH environment [35].”
BackgroundCellular point-of-care diagnostics using an inexpensive layer-stack microfluidic device
Lucas, K., Oh, J., Hoelzl, J., & Weissleder, R. (2022) · Lab on a Chip · doi:10.1039/d2lc00162d · Cited by 11
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Zhang, Q., Wang, C., Qin, M., Ye, Y., Mo, Y., Meng, Q., Guanglin, Y., Feng, G., Lin, R., Xian, S., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1298087 · Cited by 10
Dendritic cell-based immunotherapy in non-small cell lung cancer: a comprehensive critical review
de Oliveira, J. B., Silva, S. B., Fernandes, I. L., Batah, S. S., Herrera, A. J. R., Cetlin, A. A., & Fabro, A. T. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1376704 · Cited by 11
Campbell, M. J., Wolf, D. M., Yau, C. S. F., Swigart, L. B., Wulfkuhle, J., Gallagher, R. I., Zhu, Z., Bolen, J., VandenBerg, S. R., Hoyt, C. C., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101799 · Cited by 10
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Ying, S., Liu, H., Zhang, Y., & Mei, Y. (2025) · Vaccines · doi:10.3390/vaccines13050496 · Cited by 10
“Additionally, DCs secrete IL-12, which activates NK cells, further amplifying anti-tumor immune responses [35].”
Krishnan, S., Lee, S., Amoozgar, Z., Subudhi, S., Kumar, A. S., Posada, J. M., Lindeman, N. I., Lei, P., Duquette, M. A., Steinbuch, S. C., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2414941122 · Cited by 10
Resident Memory T Cells in the Tumor Microenvironment
Williams, J. B., & Kupper, T. S. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-49270-0_3 · Cited by 11
Singh, M., & Venkatas, J. (2022) · Current Cancer Drug Targets · doi:10.2174/1568009622666220609115109 · Cited by 9
Hao, S., Zhang, X., Han, L., Ma, X., Nie, Y., Deng, J., Zhu, H., Liu, Q., Ai, D., Chen, Y., et al. (2022) · Radiation Research · doi:10.1667/rade-22-00061.1 · Cited by 10
“PD-1 inhibitor inhibited adaptive immune resistance and activated intratumoral dendritic cells through IFN-c released from drug-activated T cells (25, 26).”
BackgroundSun, W., Li, Y., Sui, D., Qi, Z., Zhao, X., Zhou, W., Hu, H., Liu, X., Song, Y., & Deng, Y. (2023) · Biomaterials Science · doi:10.1039/d2bm01769e · Cited by 10
Self-assembled peptide/polymer hybrid nanoplatform for cancer immunostimulating therapies
Khazaei, S., Varela‐Calviño, R., Rad‐Malekshahi, M., Quattrini, F., Jokar, S., Rezaei, N., Balalaie, S., Haririan, I., Csaba, N., & García-Fuentes, M. (2023) · Drug Delivery and Translational Research · doi:10.1007/s13346-023-01410-y · Cited by 10
“As mentioned earlier, activated DCs produce IFN-γ, which initiate the T cell-DC crosstalk and thereby elicit T-cell priming [78].”
BackgroundMechanisms of action for different checkpoint inhibitors
Berraondo, P. (2019) · HemaSphere · doi:10.1097/hs9.0000000000000244 · Cited by 10
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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