M-MDSC activation and differentiation in tumor microenvironment. M-MDSC can differentiate into M1-like phenotype (controlled by TLR ligands, C5a, INFγ, IL-12, and IL-1β), which have antitumor effect through the production of iNOS. Alternatively, M-MDSC can differentiate into M2-like phenotype (controlled by IL-10, IL-6, TGF-β, IL-13, and IL-4), which promotes tumor growth, tissue remodeling and angiogenesis through producing IL-10 and arginase. In addition, the expansion of MDSC population can be controlled by VEGF, GM-CSF, G-CSF, M-CSF, SCF1, prostaglandins, S100A8/A9, and FLT3
Activation of M-MDSC by these factors leads to the signaling of
various pathways in differentiation of MDSC as summarized in
Fig. 3. .
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