CD226 and cancer: NK cells mediate the anti-tumor cytotoxicity through two main mechanisms: (i) on the one hand, the recognition of ligands expressed on cancer cells by NK-cell-activating receptors, such as NKG2D and DNAM-1, which triggers lytic granule production; and (ii) on the other hand, the recognition of death receptors expressed on cancer cells by NK cells’ apoptotic ligands, which triggers the apoptotic signaling [5].