One major pathway involves TGF-β (Transforming Growth Factor Beta), abundantly secreted by tumor cells, which suppresses NK activity via TGFβR2 (TGF-β receptor II); targeted deletion of TGFβR2 restore cytotoxic and improve NK cell performance in the TME [77–79] (Fig. 2g). This evidence concerns the gene TGFBR2 and neoplasm.