The downregulation of NK cell activating receptors in the periphery may result in diminished anti-tumor responses and can be reversed by ex vivo activation of NK cells expressing DNAM-1 and NKG2D, that have been shown to efficiently target and kill Ewing sarcoma (EWS), rhabdomyosarcoma (RMS) and osteosarcoma cell lines (derived from patient tumor samples) in vitro (27, 63, 64). This evidence concerns the gene CD226 and osteosarcoma.