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TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy
Open accessAbstract
SUMMARY Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer’s disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2−/− mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.
Overview
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Written from the paper’s full text.
TL;DR
TREM2 deficiency or anti-TREM2 antibody treatment restricts tumor growth and strongly enhances anti-PD-1 immunotherapy in mouse sarcoma and colorectal cancer models. TREM2 marks tumor-infiltrating macrophages in over 200 human cancers and correlates with worse survival in colorectal carcinoma and triple-negative breast cancer.
Key findings
- Trem2−/− mice were more resistant than WT mice to MCA/1956 sarcoma, MC38 colorectal cancer, and PyMT mammary tumors; with suboptimal anti-PD-1 started on day 8, 40% of WT mice rejected MCA/1956 versus 100% of Trem2−/− mice, and all Trem2−/− mice controlled MC38 growth versus only a few WT mice.
- Anti-TREM2 mAb 178 alone gave significant but incomplete tumor control, while anti-TREM2 plus suboptimal anti-PD-1 conferred complete tumor control in all mice tested; anti-TREM2 treatment attenuated tumor growth more than Trem2 deficiency, and did not further attenuate growth in Trem2−/− mice.
- scRNA-seq showed that TREM2 deletion and anti-TREM2 treatment reduced MRC1+ and CX3CR1+ macrophage subsets and expanded immunostimulatory myeloid subsets; anti-TREM2 induced de novo Nos2-Macs-t and reduced Mrc1-Macs-t, Cycling-Macs-t, and Macs1-t.
- TREM2 was expressed in tumor macrophages in over 200 human cancer cases, including 75% of carcinomas in a 126-sample tissue microarray and virtually all 99 whole tumor sections; TREM2 expression inversely correlated with overall survival in CRC and with overall and relapse-free survival in TNBC.
Methods
- Mouse tumor models included MCA/1956 sarcoma, MC38 colorectal cancer, and PyMT mammary tumors in WT and Trem2−/− mice, with anti-PD-1, Fc-mutated anti-TREM2 mAb 178, control antibodies, CD4/CD8 depletion, flow cytometry, immunofluorescence, and ex vivo T cell cytokine analysis.
- scRNA-seq was performed on live CD45+ cells sorted from MCA/1956 tumors at day 10; genotype comparison averaged 19,758 cells with 13,545 UMI per cell, and antibody-treatment comparison averaged 2,726 cells per condition with 14,622 UMI per cell, analyzed with Seurat and UMAP.
- Human analyses used FFPE tissues including a multi-tumor tissue microarray of 126 samples, primary carcinomas (n = 99), tumor-draining lymph nodes (n = 33), and distant metastases (n = 12), plus TCGA survival and correlation analyses.
Limitations
- The paper states that mechanisms by which TREM2 deficiency and anti-TREM2 treatment impact tumor macrophages remain unclear, that future biochemical experiments are needed, and that variability was noted in T cell expansion and effector function between Trem2−/− and anti-TREM2-treated mice.
- The paper states that the anti-PD-1 regimen used was suboptimal and initiated late, and that TREM2’s survival association was not significant in other tumor types, suggesting context specificity.
- Evident from the text: several experiments were performed once or with small n, scRNA-seq used n = 2 per condition in one experiment, and human evidence is largely IHC/correlation without functional validation; combined anti-TREM2 plus anti-PD-1 cleared tumors, so no infiltrate could be analyzed in that group.
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Claims the paper makes
60 Own result · 14 Own interpretation · 6 Partly supported · 6 No full text of the sources · 5 Own method · 4 Supported · 4 No basis given · 1 Couldn’t confirm · 1 Sources not found · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Trem2−/− macrophages were shown to present antigens to T cells more effectively than WT macrophages in vitro (Ito and Hamerman, 2012).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
What the sources say
- Partly supportedcites Ito and Hamerman, 2012 sourceExperimental — accuracy not yet measured
The Results section (“TREM-2 negatively regulates antigen-specific T cell proliferation by BMDCs”; page unavailable) reports that TREM-2-deficient bone-marrow-derived dendritic cells induced more antigen-specific T-cell division than WT dendritic cells in vitro. The cited experiment did not test macrophages, so the claim attributes the finding to the wrong cell type. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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In the paper
“We have previously shown that TREM2 cooperates with CSF-1 in sustaining macrophage proliferation and survival (Ulland et al., 2017).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
What the sources say
- Partly supportedcites Ulland et al., 2017 sourceExperimental — accuracy not yet measured
The Results section on macrophage mTOR signaling shows that TREM2-deficient bone marrow-derived macrophages have impaired mTOR signaling and increased autophagy when CSF1 is limiting. The Discussion says TREM2-supported mTOR signaling promotes survival and proliferation in microglia, but the cited passages do not establish that TREM2 cooperates with CSF1 to sustain macrophage proliferation and survival. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“We have previously shown that TREM2 is induced in human monocytes and mouse bone marrow cells upon exposure to GM-CSF and CSF-1 (Bouchon et al., 2001; Turnbull et al., 2006).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
What the sources say
- Partly supportedcites Bouchon et al., 2001 sourceExperimental — accuracy not yet measured
The Results section on immature monocyte-derived dendritic cells reports high TREM-2 expression after human monocytes were cultured with GM-CSF and IL-4. It does not report induction in mouse bone marrow cells or by CSF-1; in fact, TREM-2 was undetectable in human monocyte-derived macrophages cultured with M-CSF. No page number is available in our copy. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites Turnbull et al., 2006 source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
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 also re-clustered lymphoid cells, revealing heightened expression of activation markers, such as IFNγ and PD-1 (Pdcd1), by T cells and NK cells in Trem2−/− MCA tumors (Figures S2F–S2I).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Lack of TREM2 Impacts Tumor Myeloid and Lymphoid Landscape
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“TREM2 expression inversely correlated with overall survival and relapse in these cancer patients.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“PD-1+ CD4 T cells were only increased in Trem2−/− mice treated with anti-PD-1 (Figure 4F).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Enhances Checkpoint Blockade
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“On the other hand, the Macs1-g cluster, which expressed genes previously associated with IFN-γ imprinting and immunostimulation (Cxcl9 and Cd83) was much more predominant in Trem2−/−MCA tumors.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Lack of TREM2 Impacts Tumor Myeloid and Lymphoid Landscape
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Once again, tumor growth was more limited in Trem2−/− mice than in WT mice (Figures S1G and S1H).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Delays Growth of Transplanted Tumors and Modifies Tumor-Immune Infiltrate
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“however, the relative proportion of a Ly6C+MHCIIlow/− subset was significantly reduced in the Trem2−/− infiltrates (Figure 1C)”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Delays Growth of Transplanted Tumors and Modifies Tumor-Immune Infiltrate
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A 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
“Interestingly, tumor growth was more attenuated in anti-TREM2-treated mice than in Trem2−/− mice (Figure 5C).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Probably not a substantial claim. 19
- It may state two separate claims as one. 27
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TREM2 is an activating receptor of the Ig-superfamily that binds lipids and transmits intracellular signals through the adaptor DAP12 (Peng et al., 2010; Ulland et al., 2017).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Partly supportedcites Peng et al., 2010 sourceExperimental — accuracy not yet measured
The Introduction identifies TREM2 as an immunoglobulin-like, DAP12-associated receptor, and the Discussion describes signaling through the TREM2–DAP12 pathway. The Discussion says specific endogenous ligands for TREM2 were not yet known; this paper does not establish that TREM2 binds lipids. Page numbers are unavailable in our copy. (LLM, conf=0.89)
- Partly supportedcites Ulland et al., 2017 sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says TREM2 recognizes phospholipids and transmits intracellular signals through DAP12 and DAP10; the Discussion describes it as an innate immune receptor involved in signaling. Our copy does not identify TREM2 as a member of the Ig-superfamily, so that part of the attributed description is unsupported. (LLM, conf=0.87)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In the liver, a TREM2+CD9+ subset of macrophages that differentiate from circulating monocytes expands during liver cirrhosis and contributes to fibrosis (Ramachandran et al., 2019).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Supportedcites Ramachandran et al., 2019 source
The Results section, under “Pro-fibrogenic phenotype of scar-associated macrophages,” states that TREM2+CD9+ macrophages derive from recruited circulating monocytes and have a pro-fibrogenic phenotype. The Results also report that these cells expand in cirrhotic livers and promote collagen expression by hepatic stellate cells. Page numbers are not provided in the supplied passages. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In the adipose tissue, TREM2 sustains the presence of a population of lipid-associated macrophages (LAMs) that prevent the dysmetabolism engendered by a high-fat diet (Jaitin et al., 2019).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Supportedcites Jaitin et al., 2019 source
The Results section on adipose tissue macrophage remodeling reports that, after high-fat-diet feeding, Trem2-deficient mice failed to accumulate LAMs. The Results section on metabolic homeostasis reports adipocyte hypertrophy, glucose intolerance, and other metabolic abnormalities in those mice; the Discussion says Trem2-driven LAM formation prevents adipocyte hypertrophy and loss of systemic lipid homeostasis under obese conditions. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“TREM2+ macrophages have also been reported in tumors (Lavin et al., 2017; Song et al., 2019), but the impact of TREM2 in tumor immune responses has not been addressed.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Supportedcites Lavin et al., 2017 source
The Results section, under “Paired immune cell mapping reveals a distinct macrophage signature in lung adenocarcinoma,” identifies TREM2 as up-regulated in a tumor-associated macrophage cluster. This supports the cited claim that TREM2+ macrophages have been reported in tumors; the sentence’s separate statement about their impact is not attributed to this source. (LLM, conf=0.93)
- Supportedcites Song et al., 2019 source
The Discussion (page not provided) reports TREM2 among the genes upregulated during the monocyte-to-M2 macrophage transition within the intratumoral myeloid population. This supports the cited claim that TREM2+ macrophages have been reported in tumors. (LLM, conf=0.93)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“DAP12 recruits the protein tyrosine kinase Syk, which initiates a cascade of tyrosine phosphorylation events that activate downstream mediators such as PLCγ2, PI-3K, Vav, mTOR, and MAPK, ultimately leading to cell activation (Peng et al., 2010; Ulland et al., 2017).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Partly supportedcites Peng et al., 2010 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) describes a TREM2–DAP12 signaling complex containing Syk and PI3K p85, and reports activation of PLC-γ2, Vav3, and ERK1/2, a MAPK, in pathways involved in cell activation. It does not identify mTOR as a downstream mediator or establish the entire sequence as a Syk-initiated phosphorylation cascade. (LLM, conf=0.88)
- Partly supportedcites Ulland et al., 2017 sourceExperimental — accuracy not yet measured
The Introduction states that TREM2-associated DAP12 recruits Syk, while DAP10 recruits PI3-K. The Results link TREM2 signaling to PI3-K and mTOR, but the cited passages do not establish the claimed Syk-initiated tyrosine-phosphorylation cascade or identify PLCγ2, Vav, and MAPK as its downstream mediators. Page numbers are not available in our copy. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“TREM2+ tumor macrophages co-expressed CD68, CD163, CSF1R, and nuclear MAFB; foamy TREM2+ tumor macrophages also co-expressed MITF, a transcription factor involved in lysosomal biogenesis that marks a regulatory myeloid subset of human placenta (Costa et al., 2017).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Trem2 Is Selectively Expressed in Human Tumor Macrophages
What the sources say
- Supportedcites Costa et al., 2017 source
The Results section reports higher MITF expression in the placental HLA-DRhigh myeloid subset, describes MITF as involved in lysosomal biogenesis, and characterizes that subset as having tolerogenic potential. The citation supports the description of MITF and the placental subset; the sentence does not attribute its tumor-macrophage observations to Costa et al. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TREM2-signaling pathways, which include not only proliferation and survival, but also metabolism, migration and chemokine production (Peng et al., 2010; Ulland et al., 2017).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
What the sources say
- Partly supportedcites Peng et al., 2010 sourceExperimental — accuracy not yet measured
The Results section on SHIP1 and TREM2/DAP12 signaling reports survival signaling, and the Discussion proposes a link between DAP12 signaling and increased proliferation. The paper reports actin reorganization, but does not establish migration; the passages found do not address metabolism or chemokine production. Page numbers are unavailable in our copy. (LLM, conf=0.88)
- Partly supportedcites Ulland et al., 2017 sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) links TREM2 signaling to metabolism, survival, proliferation, and microglial clustering around plaques. Clustering may relate to migration, but the passages do not establish migration as a signaling outcome, and they do not support the claim about chemokine production. (LLM, conf=0.86)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“iNOS2, which has been associated with immunostimulation (Hibbs et al., 1987; Murray et al., 2014; Stuehr and Nathan, 1989), as well as immunosuppression (Shi et al., 2001).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Hibbs et al., 1987 source
- Could not verifycites Murray et al., 2014 sourceExperimental — accuracy not yet measured
The Background to the problem (p. 4) discusses macrophage activation and arginine metabolism, but does not link iNOS2 to immunostimulation. Searches for iNOS, NOS2, and nitric oxide did not locate a passage in our copy making that association. In the citing sentence, immunosuppression is attributed to Shi et al. (2001), not to this source. (LLM, conf=0.71)
- Not matchedcites Stuehr and Nathan, 1989
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A 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
“Indeed, all Trem2−/− mice controlled tumor growth as opposed to only a few WT mice (Figures 4D and 4E).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Enhances Checkpoint Blockade
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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.
In the paper
“Upon depletion of CD8+ T cells (Figure 1E), but not CD4+ T cells (Figure S1C), tumor growth was no longer attenuated, but in fact accelerated in Trem2−/− mice.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Delays Growth of Transplanted Tumors and Modifies Tumor-Immune Infiltrate
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Moreover, TREM2 was expressed in all macrophage clusters, although at different levels, while it was absent in DCs and lymphoid cells (Figure S2E).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Lack of TREM2 Impacts Tumor Myeloid and Lymphoid Landscape
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“However, analysis of T cell cytokine production ex vivo indicated that anti-TREM2 treatment augments IFNγ and TNFα production by intra-tumoral CD8+ and CD4+ T cells, respectively (Figure 5E).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“One of the macrophage subsets that recently immigrated into the tumor, Macs1-t, also declined, while the other one—Macs2-t—expanded, perhaps reflecting changes in the intratumoral differentiation of blood-derived monocytes.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Reshapes the Intratumoral Macrophages Infiltrate
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
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
“Both native and Fc mutated mAb 178 inhibited HDL-induced EGFP expression, indicating that mAb 178 blocks ligand binding to TREM2 (Figure S3B).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“At a later time point (24 days after tumor injection), in parallel with a considerable shrinkage of the tumor volume, anti-TREM2 alone showed a significant impact on the myeloid compartment: while the total number of macrophages was unchanged, the representation of Ly6ClowMHCII− cells, along with subsets expressing CD206, CD63, and CD9, was reduced (Figure S3E).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A 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
“Following this treatment protocol, only 40% of WT mice rejected the tumor, whereas 100% of Trem2−/− mice did (Figures 4B and 4C).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Enhances Checkpoint Blockade
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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It 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
“scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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.
In the paper
“We noticed that CX3CR1-Macs-g, Mrc1-Macs-g, Cycling-Macs-g, and Macs3-g were relatively meagerly represented in Trem2−/− tumors, whereas the Macs1-g cluster predominated (Figures S2B–S2D).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Lack of TREM2 Impacts Tumor Myeloid and Lymphoid Landscape
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It 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
“CD8+ T cells were increased in Trem2−/− mice with or without anti-PD-1, as were PD-1+ CD8 T cells, corroborating our initial results (see Figure 1C).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Enhances Checkpoint Blockade
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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 representation of TREM2+ macrophages was not affected by mAb 178 (Figure S3C), indicating no antibody-mediated depletion, consistent with lack of effector function in the mutated Fc fragment.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
hedged- Asserted: passes — The authors put it forward as true.
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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.
In the paper
“Other types of human tumors also showed a correlation between TREM2 and macrophage signature genes, but the association of TREM2 expression with patient overall or relapse-free survival was not significant (data not shown), suggesting that TREM2 impact on tumor-infiltrating macrophages and tumor immune responses might be context specific.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Correlates with Poor Disease Prognosis
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It 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
“MCA/1956 grew progressively in WT mice, but was consistently attenuated in Trem2−/− mice (Figures 1A and 1B).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > TREM2 Deficiency Delays Growth of Transplanted Tumors and Modifies Tumor-Immune Infiltrate
plaindirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Many macrophage subsets infiltrating MCA/1956 tumors express TREM2.
In the paper
“In atherosclerosis, TREM2+ macrophages are enriched in atherosclerotic lesions and specialize in lipid catabolism (Cochain et al., 2018).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Cochain et al., 2018 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that anti-TREM2 treatment induces a complex remodeling of the myeloid compartment that drives the appearance of Nos2-Macs-t and a parallel decline of Mrc1-Macs-t, Cycling-Macs-t, and Macs1-t recent immigrants.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Reshapes the Intratumoral Macrophages Infiltrate
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > Abstract
hedgedconditionaln = 200- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Yet, treatment of Trem2−/− mice with the anti-TREM2 mAb did not further attenuate tumor growth, demonstrating that anti-TREM2 treatment has no off-target effects.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > RESULTS > Anti-TREM2 Treatment Is Protective in the Sarcoma Model
boosted- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Although TREM2 is expressed on the cell surface, it is cleaved from the cell surface by metalloproteases and released as soluble TREM2 (sTREM2) (Ulland and Colonna, 2018).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Ulland and Colonna, 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“In the skin, TREM2+ dermal macrophages secrete oncostatin M, which inhibits hair growth by maintaining hair follicle stem cells in a quiescent state (Wang et al., 2019).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Wang et al., 2019 source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“TREM2 has been extensively studied in microglia for its capacity to sustain microglial responses to neurodegenerative pathologies such as Alzheimer’s disease (Ulland and Colonna, 2018).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Ulland and Colonna, 2018 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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 anti-TREM2 treatment presented here provides a novel therapeutic approach that broadens the armamentarium for myeloid cell targeting in tumors.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“During lung acute viral infection, TREM2+ macrophages release sTREM2, which inhibits apoptosis of macrophages, causing a feed-forward expansion of lung macrophages that converts acute infection into a chronic inflammatory disease (Wu et al., 2015).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > INTRODUCTION
What the sources say
- Not matchedcites Wu et al., 2015
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This study demonstrates that constitutive lack of TREM2 or anti-TREM2 treatment curbs tumor growth and leads to complete tumor regression when associated with suboptimal PD-1 immunotherapy.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
boosteddirect- Asserted: passes — The authors put it forward as true.
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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
“Cells identified as doublets or mutliplets based on gene expression signatures, when more than one cell population-specific marker gene was highly expressed in one cell, were filtered out.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > STAR★METHODS > QUANTIFICATION AND STATISTICAL ANALYSIS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Cells with mitochondrial content greater than 12.5% and with less than 1100 genes were removed.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > STAR★METHODS > QUANTIFICATION AND STATISTICAL ANALYSIS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Mice from different genotypes were cohoused from birth and separated during the experiment (the day of tumor injection).”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > STAR★METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“our extensive pathology study of human tumors suggests that TREM2 may be a particularly attractive therapeutic target”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > DISCUSSION
hedgedn = 200- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence.
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 animals were backcrossed until at least > 98% C57BL/6J confirmed by genotype wide microsatellite typing.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > STAR★METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Mice within experiments were age and sex matched.”
§ TREM2 Modulation Remodels the Tumor Myeloid Landscape, Enhancing Anti-PD-1 Immunotherapy > STAR★METHODS > EXPERIMENTAL MODEL AND SUBJECT DETAILS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Many macrophage subsets infiltrating MCA/1956 tumors express TREM2.
“These tumors have recently been shown to be infiltrated by a variety of macrophage subsets (Gubin et al., 2018), many of which express TREM2 (unpublished data).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In our previous study, a mouse TREM2 blocking antibody, with mutations in the Fc domain to prevent its recognition by the Fc receptor and complement, was developed and shown to block the binding of TREM2 and its high-avidity ligands38.”
From TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity (2025) · cites this paper as [38]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“and are known to be associated with failure of CPI targeting the PD-1/PD-L1 axis.80,81”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“we propose a model in which CyC is associated with recruitment of immunosuppressive Trem2+ macrophages,80,81 which in turn promote failure of cancer immunotherapy.”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“High-confidence Trem2+ monocytes were identified by expression of known TREM2+ monocyte markers (TREM2, APOE, CSF1R81,89), identified by gene-weighted density estimation implemented in the Nebulosa package for R.78”
From Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy (2023) · cites this paper as [81]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“This antibody is particularly useful because it can specifically demonstrate the effect of receptor TREM2 blockade without the confounding activity of antibody-dependent cellular cytotoxicity or antibody-dependent phagocytosis in vivo.”
From TREM2 promotes lung fibrosis via controlling alveolar macrophage survival and pro-fibrotic activity (2025) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“All blocking experiments were conducted with the anti-TREM2 mAb 178, which has been previously shown to block TREM2 function in vitro and in vivo (27–31).”
From Acute TREM2 inhibition depletes MAFB-high microglia and hinders remyelination (2025) · cites this paper as [27]
Self-check
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Self-check results appear here once an independent check has confirmed them.
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
A note, not an issue: for example, a cited work that was retracted only after this paper was published, which its authors could not have known.
In the paper
“Although the MCA/1956 sarcoma grows progressively in immunocompetent hosts, it retains sufficient immunogenicity to be effectively controlled by checkpoint immunotherapy with anti-PD-1 (Li et al., 2018).”
Cited work 10.1172/jci98769 · retracted 2022-03-15 · notice 10.1172/jci159825 · this paper published 2020-08
Citations
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“Although the MCA/1956 sarcoma grows progressively in immunocompetent hosts, it retains sufficient immunogenicity to be effectively controlled by checkpoint immunotherapy with anti-PD-1 (Li et al., 2018).”
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“Moreover, the macrophage subset inflated in anti-TREM2-treated mice expressed iNOS2, which has been associated with immunostimulation (Hibbs et al., 1987; Murray et al., 2014; Stuehr and Nathan, 1989), as well as immunosuppression (Shi et al.”
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“lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) (Freeman et al., 2000; Leach et al., 1996).”
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“mAb inhibiting CTLA-4 or PD-1 have been extensively shown to unleash T cell effector functions to control tumors in both mice and some cancer patients (Sharma and Allison, 2015; Topalian et al., 2015).”
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
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“mAb inhibiting CTLA-4 or PD-1 have been extensively shown to unleash T cell effector functions to control tumors in both mice and some cancer patients (Sharma and Allison, 2015; Topalian et al., 2015).”
Cited by
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“Trem2, recently shown to be expressed in immunosuppressive myeloid cells (Katzenelenbogen et al., 2020; Molgora et al., 2020), was also enriched in Myeloid-2 cluster (Figures 5B, 5C, and S7B).”
Self-citationTREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways
Wang, S., Sudan, R., Peng, V., Zhou, Y., Du, S., Yuede, C. M., Lei, T., Hou, J., Cai, Z., Cella, M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.09.033 · Cited by 471
Self-citationResistance Mechanisms to Anti-PD Cancer Immunotherapy
Vesely, M. D., Zhang, T., & Chen, L. (2022) · Annual Review of Immunology · doi:10.1146/annurev-immunol-070621-030155 · Cited by 468
Macrophages at the interface of the co-evolving cancer ecosystem
Kloosterman, D. J., & Akkari, L. (2023) · Cell · doi:10.1016/j.cell.2023.02.020 · Cited by 452
Colonna, M. (2023) · Nature Reviews Immunology · doi:10.1038/s41577-023-00837-1 · Cited by 394
Self-citationTowards targeting the breast cancer immune microenvironment
Harris, M. A., Savas, P. S., Virassamy, B., O’Malley, M. M. R., Kay, J., Mueller, S. N., Mackay, L. K., Salgado, R., & Loi, S. (2024) · Nature reviews. Cancer · doi:10.1038/s41568-024-00714-6 · Cited by 409
“cell adhesion molecule 1 (CADM1) + TREM2 + macrophages appear to be monocyte-derived, become dominant in progressing tumours and are correlated with poorer survival in TNBC 69,71 .”
Targeting TREM2 on tumor-associated macrophages enhances immunotherapy
Binnewies, M., Pollack, J. L., Rudolph, J., Dash, S., Abushawish, M., Lee, T., Jahchan, N. S., Canaday, P., Lu, E., Norng, M., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109844 · Cited by 365
Spatiotemporal Co-Dependency between Macrophages and Exhausted CD8 + T Cells in Cancer
Kersten, K., Hu, K. H., Combes, A. J., Samad, B., Harwin, T., Ray, A., Rao, A. A., Cai, E., Marchuk, K., Artichoker, J., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2022.05.004 · Cited by 357
Roles of macrophages in tumor development: a spatiotemporal perspective
Bied, M., Ho, W. W., Ginhoux, F., & Blériot, C. (2023) · Cellular and Molecular Immunology · doi:10.1038/s41423-023-01061-6 · Cited by 381
“Therefore, refinement of our strategies is needed and is on-going, as exemplified by the recent results suggesting efficacy of a combination of a TREM2-specific antibody with the widely used anti-PD-1 antibody in different cancer models [131].”
MethodTumor-associated macrophages in cancer: recent advancements in cancer nanoimmunotherapies
Kumari, N., & Choi, S. H. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-022-02272-x · Cited by 331
Timperi, E., Gueguen, P., Molgora, M., Magagna, I., Kieffer, Y., Lopez‐Lastra, S., Sirven, P., Baudrin, L. G., Baulande, S., Nicolas, A., et al. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-1427 · Cited by 323
Self-citationHow chemokines organize the tumour microenvironment
Mempel, T. R., Lill, J. K., & Altenburger, L. M. (2023) · Nature reviews. Cancer · doi:10.1038/s41568-023-00635-w · Cited by 317
“Proteolytic cleavage is mediated by the constitutive and inducible activities of metalloproteinases, a disinte-grin and metalloproteinase domain-containing protein 10 (ADAM10) and ADAM17 (ref.”
Kamerkar, S., Leng, C., Burenkova, O. V., Jang, S. C., McCoy, C., Zhang, K. X., Dooley, K., Kasera, S., Zi, T., Sisó, S., et al. (2022) · Science Advances · doi:10.1126/sciadv.abj7002 · Cited by 266
“Similarly, modulation of TAM function via TREM2 (Triggering Receptor Expressed On Myeloid Cells 2) inhibition ( 11 ) or small-molecule inhibitors of phosphatidylinositol 3-kinase (PI3K ) also relies on combination with CPI to demonstrate tumor growth regressions in preclinical models ( 12 ).”
InfluentialTargeting signaling pathways in prostate cancer: mechanisms and clinical trials
He, Y., Xu, W., Xiao, Y., Huang, H., Gu, D., & Ren, S. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01042-7 · Cited by 287
TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer
Park, M. D., Reyes-Torres, I., LeBerichel, J., Hamon, P., LaMarche, N. M., Hegde, S., Belabed, M., Troncoso, L., Grout, J. A., Magen, A., et al. (2023) · Nature Immunology · doi:10.1038/s41590-023-01475-4 · Cited by 251
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Kieler, M., Hofmann, M., & Schabbauer, G. (2021) · FEBS Journal · doi:10.1111/febs.15715 · Cited by 250
Cottam, M. A., Caslin, H. L., Winn, N. C., & Hasty, A. H. (2022) · Nature Communications · doi:10.1038/s41467-022-30646-4 · Cited by 216
Hendrikx, T., Porsch, F., Kiss, M. G., Rajcic, D., Papac-Miličević, N., Hoebinger, C., Goederle, L., Hladik, A., Shaw, L. E., Horstmann, H., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.06.004 · Cited by 220
Hepatocellular Carcinoma Immune Landscape and the Potential of Immunotherapies
Giraud, J., Chalopin, D., Blanc, J., & Saleh, M. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.655697 · Cited by 226
“The immunosuppressive activity of TAMs is mediated by various immune checkpoints, including PD-1, PD-L1, TIM-3, TREM1 and TREM2.”
BackgroundInfluentialMyeloid cell-targeted therapies for solid tumours
Goswami, S., Anandhan, S., Raychaudhuri, D., & Sharma, P. (2022) · Nature reviews. Immunology · doi:10.1038/s41577-022-00737-w · Cited by 228
Systemic vaccination induces CD8+ T cells and remodels the tumor microenvironment
Baharom, F., Ramirez-Valdez, R. A., Khalilnezhad, A., Khalilnezhad, S., Dillon, M., Hermans, D., Fussell, S. C., Tobin, K. K. S., Dutertre, C., Lynn, G. M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.10.006 · Cited by 220
Decoding the spatiotemporal heterogeneity of tumor-associated macrophages
Chu, X., Tian, Y., & Lv, C. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02064-1 · Cited by 234
“…carcinoma; EMT, epithelial -to-mesenchymal transition; ECM, Extracellular matrix; EV, extracellular vesicle; Treg cell, regulatory T cell; NCT, ClinicalTrials.gov. antibodies in conjunction with commonly used anti-PD-1 antibodies, highlighting potential new avenues for targeted therapy [176].”
BackgroundTime-resolved single-cell transcriptomics defines immune trajectories in glioblastoma
Kirschenbaum, D. S., Xie, K., Ingelfinger, F., Katzenelenbogen, Y., Abadie, K., Look, T., Sheban, F., Phan, T. S., Li, B., Zwicky, P., et al. (2023) · Cell · doi:10.1016/j.cell.2023.11.032 · Cited by 224
“40,41,64,65 These two distinct TAM populations developed through a striking bifurcation of mono-cyte-to-TAM trajectory (Figures 5A and 5B; Table S3).”
Self-citationJung, S., Hwang, B., Shin, S. Y., Park, E., Park, S., Kim, C. W., Kim, E., Choo, E. H., Choi, I. J., Świrski, F. K., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32284-2 · Cited by 219
Single-cell and spatial transcriptomics analysis of non-small cell lung cancer
Zuani, M. D., Xue, H., Park, J. S., Dentro, S. C., Seferbekova, Z., Tessier, J., Curras-Alonso, S., Hadjipanayis, A. G., Athanasiadis, E. I., Gerstung, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48700-8 · Cited by 251
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“In mouse models of cancer, TREM2 blockade resulted in TAM reprogramming and increased response to PD-1 immunotherapy (67).”
Faas, M., Ipseiz, N., Ackermann, J. A., Culemann, S., Grüneboom, A., Schröder, F., Rothe, T., Scholtysek, C., Eberhardt, M., Böttcher, M., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.09.010 · Cited by 206
Zernecke, A., Erhard, F., Weinberger, T., Schulz, C., Ley, K. F., Saliba, A., & Cochain, C. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac161 · Cited by 214
TREM2 dependent and independent functions of microglia in Alzheimer’s disease
Hou, J., Chen, Y., Grajales-Reyes, G., & Colonna, M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00588-y · Cited by 191
Self-citationLipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer
Masetti, M., Carriero, R., Portale, F., Marelli, G., Morina, N., Pandini, M., Iovino, M., Partini, B., Erreni, M., Ponzetta, A., et al. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20210564 · Cited by 202
C1q+ macrophages: passengers or drivers of cancer progression
Revel, M., Sautès‐Fridman, C., Fridman, W. H., & Roumenina, L. T. (2022) · Trends in cancer · doi:10.1016/j.trecan.2022.02.006 · Cited by 192
Immunobiology of high-grade serous ovarian cancer: lessons for clinical translation
Kandalaft, L. E., Laniti, D. D., & Coukos, G. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00503-z · Cited by 190
Trem2 promotes foamy macrophage lipid uptake and survival in atherosclerosis
Patterson, M. T., Firulyova, M. M., Xu, Y., Hillman, H., Bishop, C., Zhu, A., Hickok, G. H., Schrank, P. R., Ronayne, C. E., Caillot, Z., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00354-3 · Cited by 204
“Trem2 has been proposed as a therapeutic target for a variety of disease models, including Alzheimer’s disease 20 and cancer 54 .”
BackgroundCD300ld on neutrophils is required for tumour-driven immune suppression
Wang, C., Zheng, X., Zhang, J., Jiang, X., Wang, J., Li, Y., Li, X., Shen, G., Peng, J., Zheng, P., et al. (2023) · Nature · doi:10.1038/s41586-023-06511-9 · Cited by 182
“…), which encodes a surface marker for myeloid cells that mediates leukocyte adhesion and migration 15 , and Trem2 , which encodes a pathology-induced immune signalling hub that counteracts anti-tumour immunity 16 , resulted in specific depletion at the tumour site compared with bone marrow (Fig.”
BackgroundApolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer
Bancaro, N., Calì, B., Troiani, M., Elia, A. R., Arzola, R. A., Attanasio, G., Lai, P., Crespo, M., Gürel, B., Pereira, R., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.004 · Cited by 189
Liu, Z., Gao, Z., Li, B., Li, J., Ou, Y., Yu, X., Zhang, Z., Liu, S., Fu, X., Jin, H., et al. (2022) · OncoImmunology · doi:10.1080/2162402x.2022.2085432 · Cited by 175
Discovering dominant tumor immune archetypes in a pan-cancer census
Combes, A. J., Samad, B., Tsui, J. L., Chew, N. W., Yan, P., Reeder, G. C., Kushnoor, D., Shen, A. S., Davidson, B. R., Barczak, A. J., et al. (2021) · Cell · doi:10.1016/j.cell.2021.12.004 · Cited by 175
Linking macrophage metabolism to function in the tumor microenvironment
Jin, R., Neufeld, L. A., & McGaha, T. L. (2025) · Nature Cancer · doi:10.1038/s43018-025-00909-2 · Cited by 183
“Blockade of TREM2 in preclinical models of lung adenocarcinoma, sarcoma, ovarian cancer and GBM results in reduced tumor burden, which is further enhanced when combined with immune check-point blockade 119,120,122,123 .”
Lactate and IL6 define separable paths of inflammatory metabolic adaptation
Dichtl, S., Lindenthal, L., Zeitler, L., Behnke, K., Schlösser, D., Strobl, B., Scheller, J., Kasmi, K. C. E., & Murray, P. J. (2021) · Science Advances · doi:10.1126/sciadv.abg3505 · Cited by 169
Targeting of TAMs: can we be more clever than cancer cells?
Kzhyshkowska, J. G., Shen, J., & Larionova, I. (2024) · Cellular and Molecular Immunology · doi:10.1038/s41423-024-01232-z · Cited by 187
“The blue background covers TAM subtypes that correlate with a favorable prognosis and TAMs that cooperate with anticancer therapy colorectal cancer, lung cancer, hepatocellular carcinoma, or melanoma [80 – 85].”
Glaviano, A., Lau, H., Carter, L. M., Lee, E. H. C., Lam, H. Y., Okina, E., Tan, D. J. J., Tan, W., Ang, H. L., Carbone, D., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01634-6 · Cited by 169
Tirier, S. M., Mallm, J., Steiger, S., Poos, A. M., Awwad, M. H. S., Giesen, N., Casiraghi, N. A., Sušak, H., Bauer, K., Baumann, A., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26951-z · Cited by 148
Progress and Prospect of Immunotherapy for Triple-Negative Breast Cancer
Luo, C., Wang, P., He, S., Zhu, J., Shi, Y., & Wang, J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.919072 · Cited by 147
“Recently, Molgora and colleagues found that Trem2 mice are more cancer resistant and more responsive to anti-PD-1 immunotherapy than wild-type mice (57), and treatment with anti-TREM2 mAb combined with anti-PD-1 inhibited tumor growth and promoted tumor regression, with reduced MRC1 and CX3CR1 macrophages in the tumor…”
BackgroundClinical landscape of macrophage-reprogramming cancer immunotherapies
Rannikko, J. H., & Hollmén, M. (2024) · British Journal of Cancer · doi:10.1038/s41416-024-02715-6 · Cited by 169
“Another TREM family member, TREM2, sustains chronic in fl ammation in immunosuppressive TAM subsets [142, 143].”
Targeting MS4A4A on tumour-associated macrophages restores CD8+ T-cell-mediated antitumour immunity
Li, Y., Shen, Z., Chai, Z., Zhan, Y., Zhang, Y., Liu, Z., Liu, Y. S., Li, Z., Lin, M., Zhang, Z., et al. (2023) · Gut · doi:10.1136/gutjnl-2022-329147 · Cited by 145
Emerging strategies in targeting tumor-resident myeloid cells for cancer immunotherapy
Wang, Y., Johnson, K. C. C., Gatti-Mays, M. E., & Li, Z. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01335-y · Cited by 137
Tichet, M., Wullschleger, S., Chryplewicz, A., Fournier, N., Marcone, R., Kauzlaric, A., Homicskó, K., Deak, L. C., Umaña, P., Klein, C., et al. (2023) · Immunity · doi:10.1016/j.immuni.2022.12.006 · Cited by 140
Li, P., Kong, X., He, Y., Liu, Y., Peng, X., Li, Z., Xu, H. Y., Luo, H., & Park, J. (2022) · Military Medical Research · doi:10.1186/s40779-022-00414-y · Cited by 132
“TNF‑α tumor necrosis factor‑α, TREM2 Triggering receptor expressed on myeloid cells 2, MARCO macrophage receptor with collagenous structure, APOE apolipoprotein E, SPP1 secreted phosphoprotein 1, IL‑10 interlukin‑10, FOXO1 forkhead box O1, CXCL13 C‑”
BackgroundInfluentialControl of tumor-associated macrophage responses by nutrient acquisition and metabolism
Zhang, X., Ji, L., & Li, M. O. (2023) · Immunity · doi:10.1016/j.immuni.2022.12.003 · Cited by 136
CXCL9-expressing tumor-associated macrophages: new players in the fight against cancer
Marcovecchio, P., Thomas, G. D., & Salek‐Ardakani, S. (2021) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-002045 · Cited by 137
Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages
Kemp, S. B., Steele, N. G., Carpenter, E. S., Donahue, K. L., Bushnell, G. G., Morris, A. H., The, S., Orbach, S. M., Sirihorachai, V. R., Nwosu, Z. C., et al. (2021) · Life Science Alliance · doi:10.26508/lsa.202000935 · Cited by 129
“To our knowledge, TREM2 has not been evaluated in pancreatic cancer, but has been shown to play an immunosuppressive role in other tumor types (Katzenelenbogen et al, 2020; Molgora et al, 2020).”
BackgroundGallic acid for cancer therapy: Molecular mechanisms and boosting efficacy by nanoscopical delivery
Ashrafizadeh, M., Zarrabi, A., Mirzaei, S., Hashemi, F., Samarghandian, S., Zabolian, A., Hushmandi, K., Ang, H. L., Sethi, G., Kumar, A. P., et al. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112576 · Cited by 124
Tumor-associated macrophages are shaped by intratumoral high potassium via Kir2.1
Chen, S., Cui, W., Chi, Z., Xiao, Q., Hu, T., Ye, Q., Zhu, K., Yu, W., Wang, Z., Yu, C., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.08.016 · Cited by 123
TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma
Sun, R., Han, R., McCornack, C., Khan, S., Tabor, G. T., Chen, Y., Hou, J., Jiang, H., Schoch, K. M., Mao, D. D., et al. (2023) · Science Advances · doi:10.1126/sciadv.ade3559 · Cited by 119
“As a third approach to inhibiting Trem2 function, we used a TREM2 blocking antibody (clone: 178) that was reported to inhibit tumor growth in a mouse sarcoma model ( 15 ).”
InfluentialSelf-citationMolecular mechanisms underpinning sarcomas and implications for current and future therapy
Damerell, V., Pepper, M. S., & Prince, S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00647-8 · Cited by 120
“further demonstrated that the inhibition of TREM2, a pro-tumorigenic marker of tumor-associated macrophages, with an anti-TREM2 mAB, substantially increased the performance of anti-PD-1 treatment in a sarcoma mouse model.(206) This combination strategy is of particular interest since it effectively targets the immunos…”
BackgroundHu, S., Lu, H., Xie, W., Wang, D., Shan, Z., Xing, X., Wang, X.-M., Fang, J., Dong, W., Dai, W., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci157649 · Cited by 129
“Recent studies have shown that TREM2+ macrophages are the main subsets 514 of TAMs that mediate immune suppression and resistance to immunotherapy (45, 46), 515 confirming that targeting immune checkpoint molecules on T cells is not the only way 516 to attenuate T cell dysfunction.”
BackgroundSchlepckow, K., Morenas‐Rodríguez, E., Hong, S. Y., & Haass, C. (2023) · The Lancet Neurology · doi:10.1016/s1474-4422(23)00247-8 · Cited by 122
Jiang, M., Li, X., Zhang, J., Lu, Y., Shi, Y., Zhu, C., Liu, Y., Qin, B., Luo, Z., Du, Y., et al. (2021) · ACS Nano · doi:10.1021/acsnano.1c04068 · Cited by 116
Zhang, H., Liu, Z., Wen, H., Guo, Y., Xu, F., Zhu, Q., Yuan, W., Luo, R., Lu, C., Liu, R., et al. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03173-w · Cited by 119
Chen, J., Zhu, T., Jiang, G., Zeng, Q., Li, Z., & Huang, X. (2023) · Molecular Cancer · doi:10.1186/s12943-023-01830-x · Cited by 117
“The results were consistent with those of our previous study [20], Significantly stronger and rapid inhibition of tumor progression was observed in the CART-CEA.sBsAb-treated and CART-CEA.sPD-1-treated compared with that of the CART-CEA and CART-CEA.sTREM2 scFv-treated CRC mice, as indicated by…”
BackgroundResultInfluentialSystematic Pan-Cancer Analysis Identifies TREM2 as an Immunological and Prognostic Biomarker
Cheng, X. M., Wang, X., Nie, K., Cheng, L., Zhang, Z., Hu, Y., & Peng, W. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.646523 · Cited by 114
“Trem2 gene knockout model mice are more resistant to the growth of various cancers, and checkpoint immunotherapy can be improved by the TREM2 function of modifying tumor myeloid infiltrates (9).”
BackgroundHuggins, D. N., LaRue, R. S., Wang, Y., Knutson, T. P., Xu, Y., Williams, J. W., & Schwertfeger, K. L. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-0101 · Cited by 111
“Importantly, studies utilizing mice deficient in Trem2 have demonstrated its role in suppression of antitumor T-cell responses in numerous murinetumor models (41).”
BackgroundYang, X., Deng, B., Zhao, W., Guo, Y., Wan, Y., Wu, Z., Su, S., Gu, J., Hu, X., Feng, W., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.09.029 · Cited by 111
Research trends in pharmacological modulation of tumor‐associated macrophages
Wang, N., Wang, S., Wang, X., Zheng, Y., Yang, B., Zhang, J., Pan, B., Gao, J., & Wang, Z. (2021) · Clinical and Translational Medicine · doi:10.1002/ctm2.288 · Cited by 111
Ausejo‐Mauleon, I., Labiano, S., de la Nava, D., Laspidea, V., Zalacaín, M., Marrodán, L., García-Moure, M., González-Huarriz, M., Hervás-Corpión, I., Dhandapani, L., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.09.001 · Cited by 111
Coulton, A., Murai, J., Qian, D., Thakkar, K., Lewis, C. E., & Litchfield, K. (2024) · Nature Communications · doi:10.1038/s41467-024-49885-8 · Cited by 125
“…in diverse contexts, including in the maintenance of microglial fi tness in the context of Alzheimer disease 69 , in association with lipid-associated TAMs 70 , and furthermore, experimental data on mice shows that inhibition of TREM2 potentiates immunotherapy responseandinhibitstumourgrowth 71 .”
Neuregulin 4 suppresses NASH-HCC development by restraining tumor-prone liver microenvironment
Zhang, P., Chen, Z., Kuang, H., Liu, T., Zhu, J., Zhou, L., Wang, Q., Xiong, X., Meng, Z., Qiu, X., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.07.010 · Cited by 105
Huang, C., Wang, X., Wang, Y., Feng, Y., Wang, X., Chen, S., Yan, P., Liao, J., Zhang, Q., Mao, C., et al. (2024) · Nature Cancer · doi:10.1038/s43018-023-00691-z · Cited by 112
“…display high heterogenic-ity and many reports have attempted to elucidate these mechanisms at the single-cell level in different malignancies 12,43,44 ; however, the mechanisms underlying the crosstalk between tumor-infiltrating myeloid populations and tumor-infiltrating T cells remain undefined.”
Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy
Xia, X., Yang, Z., Lu, Q., Liu, Z., Wang, L., Du, J., Li, Y., Yang, D., & Wu, S. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02079-8 · Cited by 112
“In contrast, TREM2 (triggering receptor expressed by myeloid cell-2) decreases the number of MDSCs and TAMs, effectively enhancing the effect of anti-PD-1 immunotherapy with a prolonged half-life [83, 84].”
BackgroundImmunogenic Cell Death-Based Cancer Vaccines
Jin, M.-Z., & Wang, X.-P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.697964 · Cited by 99
“For example, myeloid cell TREM2 reprogrammed tumor microenvironement and the anti-TREM2 treatment promoted responsiveness of anti-PD-1 immunotherapy (8, 9).”
BackgroundThe tetraspan MS4A family in homeostasis, immunity, and disease
Mattiola, I., Mantovani, A., & Locati, M. (2021) · Trends in Immunology · doi:10.1016/j.it.2021.07.002 · Cited by 101
The immune cell atlas of human neuroblastoma
Verhoeven, B. M., Mei, S., Olsen, T. K., Gustafsson, K. U., Valind, A., Lindström, A., Gisselsson, D., Fard, S. S., Hagerling, C., Kharchenko, P. V., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100657 · Cited by 100
“TREM2 deficiency has been shown to attenuate tumor growth, and combining TREM2 deficiency with PD-1 antibodies caused tumors to completely regress in a sarcoma mouse model.(87) Since we detected that SEMA6D-TREM2 expression is significantly correlated with decreased survival suggesting, we suggest this interaction as…”
BackgroundSánchez-Paulete, A. R., Mateus-Tique, J., Mollaoglu, G., Nielsen, S. R., Marks, A., Lakshmi, A., Khan, J. A., Wilk, C. M., Pia, L., Baccarini, A., et al. (2022) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-21-1075 · Cited by 98
A temporal perspective for tumor-associated macrophage identities and functions
Blériot, C., Dunsmore, G., Alonso‐Curbelo, D., & Ginhoux, F. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.04.002 · Cited by 105
Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair
De Ponti, F. F., Bujko, A., Liu, Z., Collins, P. J., Schuermans, S., Maueroder, C., Amstelveen, S., Thoné, T., Martens, L., McKendrick, J. G., et al. (2025) · Immunity · doi:10.1016/j.immuni.2025.01.002 · Cited by 94
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Emerging Role of PD-1 in the Central Nervous System and Brain Diseases
Zhao, J., Roberts, A., Wang, Z., Savage, J. T., & Ji, R. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00683-y · Cited by 96
Single-cell immunology: Past, present, and future
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SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses
Christofides, A., Katopodi, X.-L., Cao, C., Karagkouni, D., Aliazis, K., Yenyuwadee, S., Aksoylar, H., Pal, R., Mahmoud, M. A. A., Strauss, L., et al. (2022) · Nature Immunology · doi:10.1038/s41590-022-01385-x · Cited by 96
Distinct roles of TREM2 in central nervous system cancers and peripheral cancers
Zhong, J., Xing, X., Gao, Y., Pei, L., Lu, C., Sun, H., Lai, Y., Du, K., Xiao, F., Yang, Y., et al. (2024) · Cancer Cell · doi:10.1016/j.ccell.2024.05.001 · Cited by 100
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“36 37 Tim-3 is expressed in T cells and myeloid cells, such as dendritic cells and macrophages, and is expected to be a target for tumor therapy.”
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Lipid scavenging macrophages and inflammation
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“Moreover, altering the landscape of TAMs by using a dual inhibitor that targets DC-SIGN and PD-1 [108], or an anti-TREM2 monoclonal antibody [137], promotes the augmentation and stimulation of T cells.”
Background
Metadata
- Authors
- Molgora, M., Esaulova, E., Vermi, W., Hou, J., Chen, Y., Luo, J., Brioschi, S., Bugatti, M., Omodei, A. S., Ricci, B., Fronick, C., Panda, S. K., Takeuchi, Y., Gubin, M. M., Faccio, R., Cella, M., Gilfillan, S., Unanue, E. R., Artyomov, M. N., Schreiber, R. D., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- University of Brescia (IT)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Colonna, Marco
- ORCID
- Molgora, Martina
- Esaulova, Ekaterina
- Vermi, William
- Hou, Jinchao
- Chen, Yun
- Luo, Jingqin
- Brioschi, Simone
- Bugatti, Mattia
- Omodei, Andrea Salvatore
- Ricci, Biancamaria
- Fronick, Catrina
- Takeuchi, Yoshiko
- Gubin, Matthew M.
- Faccio, Roberta
- Cella, Marina
- Gilfillan, Susan
- Unanue, Emil R.
- Artyomov, Maxim N.
- Schreiber, Robert D.
- Colonna, Marco
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 182
- Issue
- 4
- Pages
- 886-900.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7485282
- OpenAlex
- W3048665145
- Semantic Scholar
- f3e033b1cb47f2b00fc56e9c646a9bcdde754590
- Cited by
- 656
- References
- 65
- Citations by year
- 2026: 117 · 2025: 124 · 2024: 127 · 2023: 116 · 2022: 97 · 2021: 63 · 2020: 11
- FWCI
- 23.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- TREM2, tumor-infiltrating macrophages, anti-PD-1 therapy, cancer immunotherapy, TREM2 knockout mice, CX3CR1+ macrophages, immunosuppressive myeloid cells, T cell response
- MeSH terms
- CX3C Chemokine Receptor 1, Animals, Antibodies, Monoclonal, Disease Models, Animal, Humans, Immunotherapy, Membrane Glycoproteins, Methylcholanthrene, Mice, Inbred C57BL, Neoplasms, Prognosis, Receptors, Immunologic, Lymphocytes, Tumor-Infiltrating, Mice, Knockout, Cell Line, Tumor, Mice, Tumor Microenvironment, Programmed Cell Death 1 Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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