Myeloid‐Derived Suppressor Cells

Abstract Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitor cells and immature myeloid cells (IMCs) with a potent immunosuppressive activity against T‐cell responses. In health, IMCs differentiate into mature granulocytes, macrophages and dendritic cells, and these IMCs can be detected at low levels in circulation. However, different pathological conditions including cancer, infection, transplantation, autoimmune diseases and inflammation cause a disruption in the differentiation pathway of IMCs, leading to their accumulation. MDSCs exert their immunosuppressive function through the increased activity of immunosuppressive factors such as arginase‐1 and inducible nitric oxide synthase (iNOS), in addition to the increased production of nitric oxide (NO) and reactive oxygen/nitrogen species (ROS/RNS), and by modulating the production of various cytokines. The role of MDSCs in regulation of immune responses in both health and disease makes them an attractive therapeutic target in conquering various human diseases. Key Concepts MDSCs are a heterogeneous population of immature myeloid cells. Much of our understanding of MDSCs came from cancer studies; however, recent work highlighted their significance in many other pathological conditions. MDSCs are expanded in cancer and other pathological conditions owing to abnormal myelopoiesis. Mice MDSCs are defined by the co‐expression of GR‐1 and CD11b. Human MDSCs can be identified as CD11b+CD33+HLA‐DR−/low, and further divided into granulocytic CD14−and monocytic CD14+cells. MDSCs exhibit a potent inhibitory effect on various T‐cell functions. MDSCs exert their suppressive function through different mechanisms including expression of arginase 1 and inducible nitric oxide synthase and production of reactive oxygen species and nitric oxide. Correlations between circulating/infiltrating MDSC levels and clinical parameters are contradictory owing to the heterogeneous nature of human MDSCs. Some agents have been shown to reverse the immunosuppressive function or to directly target MDSCs for clinical benefits.