Figure 1.

Schematic representation of immunosuppressive cells in the TME. In this scheme the major immune cells involved in the anti-tumor or pro-tumor response are highlighted. TANs and TAMs secrete TGF-β, Il-10 and ARG-I, which inhibit the cytotoxic activity of NK cells and T cells. Moreover, TAMs promote the conversion of normal fibroblasts into CAFs, which in turn promote the proliferation of tumor cells. In this immunosuppressive microenvironment DCs, through the secretion of IL-10 and overexpression of IDO, prevent the activation of T cells, avoiding the recognition of the tumoral antigens expressed on MHC. Another immunosuppressive population is represented by MDSCs that inhibit the activation of T cells, and furthermore allow the activation of Tregs, in particular increasing the expression of CTLA4 on the surface of Treg themselves. Moreover, Tregs inhibit the cytotoxic functionality of the CTLs, where PD-1 and Fas are increased to inhibit the anti-tumoral response. Finally, the endothelium contributes to immunosuppression, since these cells express FasL.