Multiple mechanisms are used by MDSCs to dampen cytotoxic T cells and NK cells, such as the production of nitric oxide (NO) and reactive oxygen species (ROS), secretion of immunosuppressive cytokines (IL-10 and TGFβ), expression of ARG1, indoleamine 2, 3-dioxygenase, and immune checkpoint molecules (PD-L1 and CTLA-4), differentiation into suppressive TAMs (mostly from M-MDSCs).401,402 The differentiation, activation, and survival of MDSCs are regulated by tumor-derived factors (e.g., GM-CSF, IL- 6, and IL-1β), followed by methylation remodeling of DNA/RNA/protein. This evidence concerns the gene TGFB1 and neoplasm.