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

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, natural killer cells, and dendritic cells, while promoting regulatory T cells, tumor-associated macrophages, and helper T cell 17. Beyond immune suppression, MDSCs facilitate tumor angiogenesis, tumor cell stemness, epithelial-mesenchymal transition, and pre-metastatic 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, monoclonal antibodies, 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 anti-tumor responses.