Within the tumor microenvironment, different immune suppressor cells (including Tregs and MDSCs), tumor-associated fibroblasts (TAF), and tumor cells can produce soluble factors (TGF-β, PGE2, IDO-derived kynurenine) which inhibit expression and function of the major activating receptors (89, 90). This evidence concerns the gene TGFB1 and neoplasm.