Myeloid-derived Suppressor Cells (MDSC)

Cancer Immunotherapy
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Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors, immature granulocytes, macrophages, and dendritic cells at different stages of differentiation. These cells are of great interest because they have the capacity to suppress both the cytotoxic activities of natural killer (NK) and NKT cells, and the adaptive immune response mediated by CD4⁺ and CD8⁺ T cells. While the mechanism of NK cell inhibition is currently not well-understood, multiple pathways are responsible for MDSC-mediated T cell suppression including: 1) production of arginase 1/ARG1 and 2) upregulation of nitric oxide synthase 2 (NOS2). ARG1 and NOS2 metabolize L-arginine and either together, or separately, block translation of the T cell CD3 zeta chain, inhibit T cell proliferation, and promote T cell apoptosis. Additionally, MDSCs secrete immunosuppressive cytokines and induce regulatory T cell development. In mice, MDSCs are broadly defined as CD11b⁺Gr-1/Ly-6G⁺ cells, but the relative expression levels of Ly-6G and Ly-6C identify two specific subsets. Human MDSCs commonly express Siglec-3/CD33 and lack lineage markers and HLA-DR, but heterogeneous expression of CD14 and CD15 suggest that multiple subsets exist.

MDSCs are induced by pro-inflammatory cytokines and are found in increased numbers in infectious and inflammatory pathological conditions. They accumulate in the blood, bone marrow, and secondary lymphoid organs of tumor-bearing mice and their presence in the tumor microenvironment has been suggested to have a causative role in promoting tumor-associated immune suppression. Although it is now evident that MDSCs may serve as a target for preventing tumor progression, further characterization is necessary to determine how MDSCs can be identified, how they accumulate, and effective mechanisms by which they can be inhibited. R&D Systems offers a wide range of reagents useful for the characterization and functional analysis of MDSCs.