Monocytic myeloid-derived suppressor cell (M-MDSC)

Monocytic myeloid-derived suppressor cells (M-MDSCs) are a heterogeneous population of immature myeloid cells that pathologically expand during cancer, chronic infection, and inflammation to suppress immune responses [Gabrilovich, 2017; PMID: 28540004]. In humans, they are phenotypically identified as CD11b+ CD14+ HLA-DR-/low CD15- cells, distinguishing them from polymorphonuclear MDSCs and mature monocytes [Bronte et al., 2016; PMID: 27144244]. M-MDSCs exert potent immunosuppressive effects primarily by inhibiting T-cell activation and proliferation through the upregulation of Arginase-1, which depletes essential L-arginine, and the production of nitric oxide (NO) and immunosuppressive cytokines like IL-10 and TGF-beta [Veglia et al., 2018; PMID: 29942080].\n\nIn the tumor microenvironment, M-MDSCs contribute to immune evasion, promote tumor angiogenesis, and facilitate the formation of pre-metastatic niches, making them a high-priority target for cancer immunotherapy. Current pharmacological approaches do not target a single receptor but rather aim to deplete the M-MDSC population, block their recruitment from the bone marrow (e.g., via CSF1R or CCR2 inhibition), or force their differentiation into mature, non-suppressive cells using agents like all-trans retinoic acid [Law et al., 2020; PMID: 32664639]. While M-MDSCs are significant therapeutic 'targets' in a broad cellular sense, they are categorized as a cell population rather than a specific molecular receptor or enzyme.

Other names

Monocytic MDSCMo-MDSCImmature monocytic cellPathologically activated monocyte

Therapeutic strategies target M-MDSCs through four primary mechanisms: 1) Selective depletion of the cell population using low-dose chemotherapeutics like Gemcitabine or 5-Fluorouracil; 2) Inhibition of MDSC recruitment and migration from the bone marrow to the tumor site via blockade of the CCL2-CCR2 or CSF1-CSF1R axes; 3) Induction of differentiation into mature, non-suppressive myeloid cells (e.g., dendritic cells or macrophages) using agents such as ATRA; and 4) Inhibition of their suppressive metabolic functions by targeting enzymes like Arginase-1 or Phosphodiesterase-5 [Veglia et al., 2021; PMID: 33502990].