TGFβ is also the most potent suppressor of immune system activity against cancer cells in the TME, with effects mediated through stimulation of CD4+ regulatory T-cells (Tregs), suppression of cytotoxic CD8+ T-lymphocytes (CTLs) and natural killer (NK) cells, the polarization of macrophages to M2 cells, infiltration and differentiation of fibroblasts into CAFs [229]. This evidence concerns the gene CD8A and cancer.