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Background <p>Tumor-associated macrophages are key players in cancer progression, but their heterogeneity is not fully understood. This study aims to investigate the role of a specific macrophage subpopulation marked by LY6E in esophageal squamous cell carcinoma (ESCC).</p> Methods <p>We analyzed macrophage subsets in ESCC, focusing on LY6E<sup>+</sup> populations. Their gene expression signature, functional characteristics, and correlation with patient prognosis and immunotherapy response were assessed through single cell RNA sequencing and multiplex immunohistochemistry.</p> Results <p>A distinct LY6E<sup>+</sup> macrophage subpopulation was identified, enriched in tumors and associated with poor prognosis. These cells exhibited an M2-like, immunosuppressive phenotype, yet possessed high phagocytic and antigen-presenting potential. A potential niche involving LY6E<sup>+</sup> macrophages, exhausted CD8<sup>+</sup> T cells, and ICAM2<sup>+</sup> tumor cells was discovered, which predicted a better response to immunotherapy.</p> Conclusions <p>Our findings reveal a critical and complex role for LY6E<sup>+</sup> macrophages in ESCC, highlighting them as a potential target for therapeutic intervention.</p>

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Identification of a distinct cluster of LY6E+ macrophages in esophageal squamous cell carcinoma: functional phenotype, spatial interaction, and prognostic significance

  • 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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  • Kun Chen,
  • Jianjiao Ni,
  • Yida Li,
  • Sijia Gu,
  • Ye Li,
  • Xi Yang,
  • Shyamal Goswami,
  • Qiyu Luo,
  • Yalei Zhang,
  • Ling Qian,
  • Yudi Hu,
  • Runye Zhou,
  • Yating Wang,
  • Jingjing Liu,
  • Xiuyu Cai,
  • Chunrong Zhang,
  • Saifullah Afridi,
  • Yi Chen,
  • Peng Wang,
  • Zhengfei Zhu

摘要

Background

Tumor-associated macrophages are key players in cancer progression, but their heterogeneity is not fully understood. This study aims to investigate the role of a specific macrophage subpopulation marked by LY6E in esophageal squamous cell carcinoma (ESCC).

Methods

We analyzed macrophage subsets in ESCC, focusing on LY6E+ populations. Their gene expression signature, functional characteristics, and correlation with patient prognosis and immunotherapy response were assessed through single cell RNA sequencing and multiplex immunohistochemistry.

Results

A distinct LY6E+ macrophage subpopulation was identified, enriched in tumors and associated with poor prognosis. These cells exhibited an M2-like, immunosuppressive phenotype, yet possessed high phagocytic and antigen-presenting potential. A potential niche involving LY6E+ macrophages, exhausted CD8+ T cells, and ICAM2+ tumor cells was discovered, which predicted a better response to immunotherapy.

Conclusions

Our findings reveal a critical and complex role for LY6E+ macrophages in ESCC, highlighting them as a potential target for therapeutic intervention.