Myeloid-Derived Suppressor Cells: Orchestrators of Tumor Immune Evasion and Therapeutic Vulnerabilities.

Abstract

Myeloid-derived suppressor cells (MDSCs) are characterized by abnormal phenotypes, high heterogeneity, and immunosuppressive function. MDSCs are critical components in the tumor immune microenvironment, contributing to cancer progression by inhibiting T cells, B cells, NK cells, and dendritic cells while promoting regulatory T cells, tumor-associated macrophages, and Th17 cells. Beyond immunosuppression, MDSCs facilitate tumor angiogenesis, tumor cell stemness, epithelial-mesenchymal transition, and premetastatic niche formation. Current therapeutic strategies targeting MDSCs include depletion, functional inhibition, induction of differentiation, and disruption of MDSC recruitment and activation. Various therapeutic agents-including chemotherapeutics, mAbs, small-molecule inhibitors, and natural compounds-have shown efficacy in modulating MDSC activity. Combining MDSC-targeted therapy with existing immunotherapies, such as immune checkpoint inhibitors, may further improve antitumor responses.