Although the response rates to ICIs in patients with melanoma is improving, around half of melanoma patients still do not respond combination anti-PD-1/anti-CTLA-4 therapies, whilst single agent response rates are even lower at ~ 30–40% for anti-PD-1 agents and ~ 10–15% for anti-CTLA-4 agents [91–93]. This evidence concerns the gene PDCD1 and melanoma.