ICIs targeting the programmed cell death 1 protein (PD-1) and programmed death ligand 1 (PD-L1), alone or in combination with the cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), are now used as first-line therapy for late-stage cancers, including metastatic melanoma (MM), non–small cell lung cancer (NSCLC), and renal cell carcinoma (RCC). The gene discussed is CTLA4; the disease is renal cell carcinoma.