The observation of melanoma patients receiving ipilimumab (anti-CTLA4 mAb) and autologous tumor cells engineered to produce GM-CSF as therapy revealed that due to the activation of NKG2D expression on NK cells and cytotoxic lymphocytes, some patients spontaneously developed antibodies against MICA, which bound sMICA from plasma and promoted opsonization of tumor cells for dendritic cell cross-presentation [89]. Here, MICA is linked to neoplasm.