Combination immunotherapy targeting both cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1) immune checkpoints has resulted in a median progression-free survival (PFS) of 11.5 months and 5-year survival rates of up to 52% in previously untreated patients with advanced melanoma.1–3 However, objective response to immune checkpoint inhibitors (ICI) is limited to 40% and evidence of clinical activity is present in up to 65% of patients.4 The gene discussed is PDCD1; the disease is melanoma.