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Identification of TREM2-positive tumor-associated macrophages in esophageal squamous cell carcinoma: implication for poor prognosis and immunotherapy modulation
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. H...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10175681/ https://www.ncbi.nlm.nih.gov/pubmed/37187751 http://dx.doi.org/10.3389/fimmu.2023.1162032 |
Sumario: | 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. METHODS 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. CONCLUSION: 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 |
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