Downregulation of activating receptors is associated with reduced expression of respective ligands on the surface of cancer cells, cancer cells production of soluble ligands blocking recognition by NK cell activating receptors, and inhibition of expression/function of NK cell receptors such as NKG2D, NKp46, NKp30, DNAX accessory molecule-1 (DNAM-1/CD226), and CD16 (FCγRIII). Here, CD226 is linked to cancer.