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

## TL;DR

This study identifies TREM1+ PMN-MDSCs as important immune suppressors in various cancers, suggesting TREM1 could be a key target for cancer therapy.

## Contribution

The study reveals TREM1+ PMN-MDSCs as conserved regulators of immunosuppression and tumor microenvironment remodeling across multiple cancers.

## Key findings

- TREM1+ PMN-MDSCs show upregulation of immunosuppressive genes and are linked to poor prognosis in multiple cancers.
- TREM1+ PMN-MDSCs are more abundant in tumor regions and co-localize with fibroblasts and exhausted T cells.
- TREM1+ PMN-MDSCs interact with various cell types to remodel the tumor microenvironment.

## 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.

A pan-cancer analysis reveals TREM1+ PMN-MDSCs as key mediators of immunosuppression by remodeling the tumor microenvironment, highlighting TREM1 as a therapeutic target.