Immunotherapies, such as anti-CTLA-4 or anti-PD-1/anti-PD-L1 antibodies, have better response rates and improvement in patient survival with advanced melanoma, but clinical trial data suggest that not all melanoma patients are responsive to single agent monoclonal antibodies for CTLA-4/PD-1/PD-L1 [386,398]. This evidence concerns the gene CTLA4 and melanoma.