The combination of CTLA-4 and PD-1 blockade in patients with advanced melanoma has demonstrated an unprecedented response rate of 58%, translating into a median overall survival rate of >5 years, and a 5-year overall survival rate of 52% (Larkin et al., 2015a, 2019; Postow et al., 2015), making this drug combination the standard of care in unresectable melanoma. This evidence concerns the gene CTLA4 and melanoma.