Abstract
There has been a great interest in myeloid-derived suppressor cells (MDSCs) due to their biological functions in tumor-mediated immune escape by suppressing antitumor immune responses. These cells arise from altered myelopoiesis in response to the tumor-derived factors. The most recognized function of MDSCs is suppressing anti-tumor immune responses by impairing T cell functions, and these cells are the most important players in cancer dissemination and metastasis. Therefore, understanding the factors and the mechanism of MDSC differentiation, expansion, and recruitment into the tumor microenvironment can lead to its control. However, most of the studies only defined MDSCs with no further characterization of granulocytic and monocytic subsets. In this review, we discuss the mechanisms by which specific MDSC subsets contribute to cancers. A better understanding of MDSC subset development and the specific molecular mechanism is needed to identify treatment targets. The understanding of the specific molecular mechanisms responsible for MDSC accumulation would enable more precise therapeutic targeting of these cells.
Highlights
Myeloid-derived suppressor cells (MDSCs) represent a population of heterogeneous myeloid lineage cells that have the potent immunosuppressive activity of T cell activation and function
Since GR-1 antibodies can bind to two separate epitopes, Ly6G and Ly6C, these epitope-specific antibodies have been used to distinguish two myeloid-derived suppressor cells (MDSCs) subsets: granulocytic MDSCs (G-MDSCs), which have a CD11b+Ly6G+Ly6Clow phenotype, whilst monocytic MDSCs (M-MDSCs) have a CD11b+Ly6G−Ly6Chigh phenotype [2]
Evidence indicates that both MDSC subsets expanded in most of the murine tumor model, but the expansion of G-MDSCs was much greater than the M-MDSCs and represented more than 80% of all MDSCs [4,5]
Summary
Myeloid-derived suppressor cells (MDSCs) represent a population of heterogeneous myeloid lineage cells that have the potent immunosuppressive activity of T cell activation and function. They comprise macrophages, granulocytes, and dendritic cells in immature stages of development. Hematopoietic stem cells give rise to myeloid progenitor and precursor cells in the bone marrow. These immature myeloid cells (IMCs) migrate to peripheral lymphoid organs and differentiate into mature granulocytes, macrophages, or dendritic cells. The frequency of circulating MDSC increases dramatically in cancer, autoimmunity, infection, always correlates with the disease severity and worsens the survival rates
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