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

Abstract 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.