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). The gene discussed is CD226; the disease is neoplasm.