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Background <p>CD172a (SIRPα) is an inhibitory receptor on myeloid cells, but its role in esophageal carcinoma (EC) remains poorly characterized. This study aimed to comprehensively investigate CD172a expression patterns, functional implications, and clinical relevance in EC.</p> Methods <p>We integrated bulk RNA-seq data from TCGA (<i>n</i> = 181) and single-cell RNA-seq data from GEO (GSE160269, 60 tumors) to analyze CD172a expression across cellular compartments. Functional enrichment and module scoring were performed to characterize CD172a-associated pathways. A validation cohort of 33 EC patients was analyzed using multiplex immunofluorescence to assess CD172a protein expression in tumor-associated macrophages (TAMs) and its association with clinicopathological features.</p> Results <p>CD172a was predominantly expressed in macrophages within the EC tumor microenvironment, with minimal expression in tumor epithelial cells. CD172a-high macrophages exhibited an M2-like immunosuppressive phenotype, characterized by upregulation of CD276, TREM2, and MMP12, and enhanced scores for immunosuppression, phagocytosis, and M2 polarization. High CD172a expression was associated with significantly poorer overall survival in EC patients (<i>p</i> &lt; 0.05), particularly in the ESCC subtype. In our validation cohort, CD172a expression in TAMs was significantly elevated in tumor tissues compared to adjacent normal tissues (<i>p</i> &lt; 0.01), and all patients with distant metastases (9/9) showed CD172a-positive macrophage infiltration.</p> Conclusion <p>CD172a marks an immunosuppressive TAM subset in EC and serves as a prognostic biomarker. These findings highlight the CD172a-CD47 axis as a potential therapeutic target for EC immunotherapy.</p>

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CD172a+ tumor-associated macrophages drive immunosuppression and predict poor prognosis in esophageal carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月29日

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  • Xiaodong Zhang,
  • Xinlei Gu,
  • Weining Gao,
  • Weipeng Shao

摘要

Background

CD172a (SIRPα) is an inhibitory receptor on myeloid cells, but its role in esophageal carcinoma (EC) remains poorly characterized. This study aimed to comprehensively investigate CD172a expression patterns, functional implications, and clinical relevance in EC.

Methods

We integrated bulk RNA-seq data from TCGA (n = 181) and single-cell RNA-seq data from GEO (GSE160269, 60 tumors) to analyze CD172a expression across cellular compartments. Functional enrichment and module scoring were performed to characterize CD172a-associated pathways. A validation cohort of 33 EC patients was analyzed using multiplex immunofluorescence to assess CD172a protein expression in tumor-associated macrophages (TAMs) and its association with clinicopathological features.

Results

CD172a was predominantly expressed in macrophages within the EC tumor microenvironment, with minimal expression in tumor epithelial cells. CD172a-high macrophages exhibited an M2-like immunosuppressive phenotype, characterized by upregulation of CD276, TREM2, and MMP12, and enhanced scores for immunosuppression, phagocytosis, and M2 polarization. High CD172a expression was associated with significantly poorer overall survival in EC patients (p < 0.05), particularly in the ESCC subtype. In our validation cohort, CD172a expression in TAMs was significantly elevated in tumor tissues compared to adjacent normal tissues (p < 0.01), and all patients with distant metastases (9/9) showed CD172a-positive macrophage infiltration.

Conclusion

CD172a marks an immunosuppressive TAM subset in EC and serves as a prognostic biomarker. These findings highlight the CD172a-CD47 axis as a potential therapeutic target for EC immunotherapy.