Identification of TREM2-positive tumor-associated macrophages in esophageal squamous cell carcinoma: implication for poor prognosis and immunotherapy modulation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37187751", "kind": "science-record", "revision": 4, "content_hash": "sha256:4561d1176be78e0538f14f5e7abf28be890eccb5337befc7ef9cba8195eb6b3f", "created_at": "2026-11-01T19:01:52Z", "updated_at": "2026-11-01T22:51:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of TREM2-positive tumor-associated macrophages in esophageal squamous cell carcinoma: implication for poor prognosis and immunotherapy modulation.", "doi": "10.3389/fimmu.2023.1162032", "pmid": "37187751", "authors": ["Hongmu Li", "Yu Miao", "Leqi Zhong", "Songjie Feng", "Yue Xu", "Lu Tang", "Chun Wu", "Xianzhou Zhang", "Ling Gu", "Hengyi Diao", "Huiyun Wang", "Zhesheng Wen", "Minglei Yang"], "journal": "Frontiers in immunology", "year": 2023, "abstract": "Background: It is now understood that the effectiveness of checkpoint immunotherapy can be impaired by immunosuppressive tumor-associated macrophages (TAMs). Nonetheless, the impact of different TAM subpopulations on the antitumor immune response remains unclear, mainly due to their heterogeneity. Herein, we identified a novel TAM subpopulation in esophageal squamous cell carcinoma (ESCC) that might contribute to poor clinical outcomes and immunotherapy modulation.\nMethods and results: We analyzed two single-cell RNA sequencing (scRNA-seq) datasets (GSE145370 and GSE160269) of esophageal squamous cell carcinoma to identify a novel TREM2-positive TAM subpopulation characterized by upregulation of TREM2, C1QC, C1QB, C1QA, SPP1, and APOE. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that these genes were significantly overexpressed in ESCC. Multiplex immunofluorescence validated the infiltration of TREM2+ TAMs in ESCC tissues, which correlated with poorer overall survival (OS). The scRNA-seq analysis in dataset GSE120575 indicated significant enrichment of TREM2+ TAMs in melanoma patients (n=48) with poor immunotherapy response, which had an identical gene signature with TREM2+ TAMs from ESCC. Analysis of 29 bulk-RNA melanoma samples from dataset GSE78220 revealed that a gene signature of 40 genes associated with TREM2+ TAMs was upregulated in the transcriptome of melanomas that did not respond to anti-PD1 therapy. Validation in the TCGA ESCC cohort (n=80) showed that a high enrichment score of the TREM2+ TAM was associated with poor prognosis. In addition, 10 ESCC patients treated with anti-PD1 therapy suggested that patients who are not sensitive to immunotherapy have higher density of TREM2+TAMs infiltration.\nConclusion: Overall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population. modulation; single-cell RNA sequencing.", "claims": [{"id": "claim-method", "statement": "Using this gene signature, we calculated the enrichment score of TREM2 + TAMs for 80 patients with ESCC via single-sample gene set enrichment analysis (ssGSEA) (28) in gene set variation analysis (GSVA) (29) in R. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimates and log-rank testing.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37187751", "locator": "sections[7] \"Identification of a high TREM2+ TAM-enriched subset of patients with ESCC\" paragraph 2", "quote": "Using this gene signature, we calculated the enrichment score of TREM2 + TAMs for 80 patients with ESCC via single-sample gene set enrichment analysis (ssGSEA) (28) in gene set variation analysis (GSVA) (29) in R."}, {"asset": "source:pmid:37187751", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimates and log-rank testing."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37187751", "locator": "sections[21] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Overall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37187751", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Overall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Overall, TREM2+ TAM infiltration in ESCC is associated with poor prognosis and may serve as a biomarker for predicting outcomes and immunotherapy modulation in this patient population.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37187751"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The scRNA-seq analysis in dataset GSE120575 indicated sign"], "order_basis": "paper_text_order:624", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ods and results: We analyzed two single-cell RNA sequencing (scRNA-seq) datasets (GSE145370 and GSE16026", "patient population. modulation; single-cell RNA sequencing.", "ated with TREM2+ TAMs was upregulated in the transcriptome of melanomas that did not respond to anti-PD"], "order_basis": "paper_text_order:636", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["QC, C1QB, C1QA, SPP1, and APOE. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent as"], "order_basis": "paper_text_order:876", "id": "assay:3"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that these genes were signific", "OE. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that these genes were s"], "order_basis": "paper_text_order:904", "id": "assay:4"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["gnificantly overexpressed in ESCC. Multiplex immunofluorescence validated the infiltration of TREM2+ TAMs in"], "order_basis": "paper_text_order:1028", "id": "assay:5"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["(CD4_Tex_Mouse) and CD8 Tex (CD8_Tex_Mouse) in mice with chronic viral infection (32), CD8 TEX i"], "order_basis": "paper_text_order:3127", "id": "assay:6"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Using this gene signature, we calculated the enrichment score of TREM2 + TAMs for 80 patients with ESCC via single-sample gene set enrichment analysis (ssGSEA) (28) in gene set variation analysis (GSVA) (29) in R. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier estimates and log-rank testing."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}