Anti-CTLA-4 inhibitors, which target regulatory T cells, and anti-PD-1/L-1 inhibitors, which target activated T-cells, dendritic cells, and tumor cells, have reshaped the management of melanoma leading to improvements in progression free and overall survival, with reports of upwards to 22% of patients experiencing complete response (CR) [3–9]. This evidence concerns the gene CTLA4 and melanoma.