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Pan-cancer analysis reveals TREM1+ PMN-MDSCs as critical regulators of immune suppression and tumor microenvironment
Yangjie Cai1, Shanhang Li2, Hening Li3
1Department of Traumatic Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
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.
Insights
Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are key to tumor immunosuppression. Targeting TREM1 on these cells may overcome immune evasion in various cancers.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) drive tumor immunosuppression.
- Their heterogeneity and spatial roles in cancer are not fully understood.
Purpose of the Study:
- To characterize PMN-MDSC populations across diverse cancers.
- To investigate the role of TREM1 in PMN-MDSC function and tumor microenvironment interactions.
Main Methods:
- Integrated single-cell RNA sequencing (scRNA-seq) from 576 cancer samples.
- Spatial transcriptomics and multiplex immunofluorescence on three malignancies.
- CellChat analysis for intercellular communication.
Main Results:
- Identified a conserved PMN-MDSC population with immunosuppressive gene signatures.
- TREM1 was highly expressed on PMN-MDSCs and associated with poor prognosis.
- TREM1+ PMN-MDSCs were enriched in tumors, co-localized with fibroblasts and exhausted T cells, and remodeled the tumor microenvironment.
Conclusions:
- TREM1+ PMN-MDSCs exhibit conserved immunosuppressive functions and spatial networks across cancers.
- TREM1 is a potential therapeutic target to disrupt tumor immune evasion.
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