Fig. 1

Stages of MDSC differentiation and accumulation. Hematopoietic stem cells (HSCs) differentiate in bone marrow into common myeloid progenitors (CMPs), which can further differentiate through the hematopoietic system. Under physiological conditions, CMPs can differentiate into neutrophils or monocytes and subsequently into MΦs or DCs. However, under pathologic conditions, immature myeloid cells (IMCs) are expanded and converted to immunosuppressive MDSCs, which include monocytic myeloid-derived suppressor cells (M-MDSCs) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). In tumors, M-MDSCs can further differentiate into tumor-associated macrophages (TAMs) (M1 and M2 phenotypes). Different cytokines are involved in the whole differentiation process. Growth factors such as SCF, G-CSF, GM-CSF, and M-CSF regulate myelopoiesis progression, inducing the expansion of MDSCs. In the presence of proinflammatory cytokines such as IFN-γ, IL-4, IL-6, IL-1β, and CXCL1, IMCs are pathologically activated and then differentiate into M-MDSCs and PMN-MDSCs. Hypoxia in the TME facilitates the expression of hypoxia-inducible factor 1-alpha (HIF-1α), which leads to MDSC recruitment and accumulation. TME, tumor microenvironment