ICOS, a T-cell costimulatory molecule of the CTLA-4/PD-1/CD28 family, plays a nonoverlapping function with CD28 [151] and is highly expressed by TA-Tregs in breast carcinoma [21,152], ovarian carcinoma [153,154], follicular lymphoma [155], melanoma [156,157], RCC [158] and gastric cancer [159]. Here, CD28 is linked to melanoma.