While it was demonstrated that TGF-β impairs effector functions of NK cells against target cells, the underlying mechanisms remained elusive until it was reported by Moretta and colleagues that TGF-β downregulates the surface expression of the activating NK receptors NKG2D and NKp30, thereby impairing NK cytolysis of tumor cell lines in vitro (103) (Figure 1). This evidence concerns the gene NCR3 and neoplasm.