Supporting the notion that NK cells exposed to a TGF-β-rich TME develop an ILC1-like state and display decreased anti-tumor functionality is the observation that NKp46+ cells from Smad4fl/fl x Ncr1iCre mice acquire ILC1 characteristics via a non-canonical SMAD4-dependent, but TGF-β-R2 independent, pathway and lose the ability to protect from lung metastases in the B16 melanoma model [23]. This evidence concerns the gene TGFBR2 and neoplasm.