The Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) molecule, first characterized by Brunet et al. in the 1980s, was the first ICI to be targeted in a clinical trial in 2000, and ipilimumab, a CTLA-4 blocking antibody, was the first ICI antibody to be approved in 2011 by the FDA for the treatment of metastatic melanoma [46,47]. Here, CTLA4 is linked to metastatic melanoma.