CTLA4 and melanoma: In the last decade, the emergence of effective systemic therapies (ESTs) in the form of both targeted and immuno-based therapies, including BRAF- and MEK-inhibitors in association with programmed cell death (PD-1) inhibitors and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), has revolutionized the treatment of patients with advanced stage III and stage IV melanoma [16,17,18], offering a four-year OS of up to 53%.