The combination therapy with anti-PD-1 and anti-CTLA-4 agents is approved by FDA for metastatic melanoma, renal cell carcinoma and microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, based on improved overall survival versus either agent alone [6-10]. The gene discussed is PDCD1; the disease is metastatic melanoma.