As in the case of other activating receptors ligands, chronic exposure to CD155 leads to reduced DNAM-1 expression, and subsequently, NK-cell-decreased responsiveness and tumour progression, as reported in ovarian cancer, glioblastoma, colorectal carcinoma, lung adenocarcinoma, melanoma, and pancreatic cancer [82,106,107,108,109,110]. This evidence concerns the gene CD226 and melanoma.