Figure 1.

Strategies of targeting MDSCs in cancers. In physiological condition, HSCs differentiate into CMPs and GMPs, which subsequently become mature granulocytes or monocytes. In pathological condition such as malignancy, multiple tumor-derived factors affect the differentiation of myeloid cells, leading to the generation M-MDSCs and PMN-MDSCs. Both types of MDSCs migrate to the tumor site through the interaction of chemokine receptors and ligands (CCLs or CXCLs). In TME, MDSCs are activated and can support tumor growth by suppressing antitumor response of T cells through various mechanisms such as ARG1, iNOS, ROS, TGF-β, IL-10, and IDO. MDSCs can also promote macrophage polarization and induce Tregs and tolerogenic DCs. Reversing the protumor effects of MDSCs could be achieved by depleting MDSCs, promoting MDSC differentiation, blocking MDSC trafficking and migration into TME, and inhibiting the immunosuppressive function of MDSCs.

Abbreviations: HSC, hematopoietic stem cells; CMP, common myeloid progenitor; GMP,granulocyte-macrophage progenitor; MDP, macrophage/dendritic cell progenitors; MDSCs,  myeloid-derived suppressor cells; M-MDSCs, monocytic myeloid-derived suppressor cells; PMN-MDSCs, polymorphonuclear myeloid-derived suppressor cells; GM-CSF, granulocyte-macrophage colony-stimulating factor; M-CSF, macrophage colony-stimulating factor; VEGF, vascular endothelial growth factor; G-CSF, granulocyte colony-stimulating factor; SCF, stem cell factor; IFN-γ, interferon-γ; PGE2, prostaglandin E2; ARG1, arginase; IDO, indoleamine 2,3-dioxygenase; NO, nitric oxide; DC, dendritic cell, T, T cell; Treg, regulatory T cell; Mϕ, macrophage; ENTPD2, ectonucleoside triphosphate diphosphohydrolase 2; CCLs, CC chemokine ligands; CXCLs, C-X-C chemokine ligands; TME, tumor microenvironment; iNOS, inducible nitric oxide synthase.