A seminal finding about MICA as target in I-O came from the observation that some melanoma patients that received ipilimumab (an anti-CTLA4 mAb) and autologous tumor cells engineered to produce GM-CSF, spontaneously developed anti-MICA Ab that promoted clearing of sMICA from plasma and opsonization of tumor cells for dendritic cell cross-presentation. Here, MICA is linked to melanoma.