SuppressorzellenMDSCs

SuppressorzellenMDSCs, or myeloid-derived suppressor cells, are a heterogeneous group of immature myeloid cells with potent immunosuppressive activity. They arise during chronic inflammation, infection, trauma, and especially cancer, where they accumulate in blood, bone marrow, spleen, and the tumor microenvironment to blunt anti-tumor immune responses.

In humans, MDSCs are commonly defined as CD11b+ CD33+ HLA-DRlow/- cells and are subdivided into monocytic MDSCs (M-MDSCs; typically CD14+) and granulocytic or polymorphonuclear MDSCs (PMN-MDSCs; CD15+/CD66b+). In mice, classical subsets are CD11b+ Gr-1+ with Ly6Chigh monocytes and Ly6G+ neutrophil-like cells. Marker expression varies with species and maturation state, and the definition often relies on functional criteria rather than a single marker set.

Suppressive mechanisms include arginase-1–mediated depletion of L-arginine, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) production, cysteine depletion, and secretion of IL-10 and TGF-β; expression of PD-L1; and indirect effects such as promoting regulatory T cells and skewing macrophages toward an M2-like phenotype. Through these pathways, they inhibit T cell proliferation and function and can dampen NK cell activity.

Clinically, elevated MDSCs associate with tumor progression, metastasis, and poorer responses to immunotherapy, as well as with chronic infections and inflammatory conditions. Therapeutic strategies aim to reduce MDSC numbers or block their function, including differentiation therapy (for example, all-trans retinoic acid), PDE-5 inhibitors, CSF-1R inhibitors, COX-2 blockade, and combination vaccination approaches.