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<p>Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are crucial mediators of tumor-induced immunosuppression, while their heterogeneity and spatial dynamics across malignancies remain poorly understood. By integrating single-cell RNA sequencing data from 576 samples across 19 cancer types and spatial transcriptomics data from three distinct malignancies, we identified a PMN-MDSC population. This cell population demonstrated characteristic upregulation of immunosuppressive genes and was associated with poor prognosis across multiple cancer cohorts. Notably, <i>TREM1</i> was highly expressed in PMN-MDSCs and may mediate immunosuppressive processes. Multiplex immunofluorescence demonstrated that <i>TREM1</i><sup>+</sup> PMN-MDSCs exhibited significantly higher distribution in tumor regions compared to non-tumor tissues. Spatial transcriptomics analysis revealed their co-localization with fibroblasts and exhausted T cells. Moreover, CellChat analysis showed that <i>TREM1</i><sup>+</sup> PMN-MDSCs remodeled the tumor microenvironment through interactions with diverse cellular components. Collectively, our study revealed the conserved immunosuppressive features and spatial interaction networks of <i>TREM1</i><sup>+</sup> PMN-MDSCs from a pan-cancer perspective, highlighting <i>TREM1</i> as a pivotal therapeutic target to disrupt PMN-MDSC-mediated tumor immune evasion.</p>

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Pan-cancer analysis reveals TREM1+ PMN-MDSCs as critical regulators of immune suppression and tumor microenvironment remodeling

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月18日

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  • Yangjie Cai,
  • Shanhang Li,
  • Hening Li,
  • Zhuan Zou,
  • Xinda Zheng,
  • Haijun Tang,
  • Mingxiu Yang,
  • Pintian Wang,
  • Weizhen Wu,
  • Hongcai Teng,
  • Kai Luo,
  • Xinyu Huang,
  • Wenyu Feng,
  • Shijie Liao,
  • Juliang He,
  • Yun Liu

摘要

Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are crucial mediators of tumor-induced immunosuppression, while their heterogeneity and spatial dynamics across malignancies remain poorly understood. By integrating single-cell RNA sequencing data from 576 samples across 19 cancer types and spatial transcriptomics data from three distinct malignancies, we identified a PMN-MDSC population. This cell population demonstrated characteristic upregulation of immunosuppressive genes and was associated with poor prognosis across multiple cancer cohorts. Notably, TREM1 was highly expressed in PMN-MDSCs and may mediate immunosuppressive processes. Multiplex immunofluorescence demonstrated that TREM1+ PMN-MDSCs exhibited significantly higher distribution in tumor regions compared to non-tumor tissues. Spatial transcriptomics analysis revealed their co-localization with fibroblasts and exhausted T cells. Moreover, CellChat analysis showed that TREM1+ PMN-MDSCs remodeled the tumor microenvironment through interactions with diverse cellular components. Collectively, our study revealed the conserved immunosuppressive features and spatial interaction networks of TREM1+ PMN-MDSCs from a pan-cancer perspective, highlighting TREM1 as a pivotal therapeutic target to disrupt PMN-MDSC-mediated tumor immune evasion.