Since the first approval of ipilimumab in 2011, immunotherapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1), its ligand (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), either as monotherapy, immunochemotherapy, or dual immuno-oncology (IO) combination therapy, has transformed the treatment landscape of many cancer types by offering durable responses in a subset of patients. The gene discussed is CTLA4; the disease is cancer.