Mainly developed to overcome resistance and toxicity associated with the anti‐cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) ipilimumab (the first checkpoint inhibitor approved by the FDA [45]), they were firstly used for metastatic melanoma [46, 47], but they have been recently approved for the treatment of several other tumors, such as non-small cell lung cancer (NSCLC), head and neck carcinoma, renal cell carcinoma (RCC), Hodgkin's lymphoma, and squamous cell lung cancer [48–51]. This evidence concerns the gene CTLA4 and metastatic melanoma.