CTLA4 and melanoma: Multiple clinical trials conducted to test the safety and efficacy of combining anti–PD-1 with anti–CTLA-4 have shown a remarkable increase in response rate and median survival time in multiple cancers, including melanoma, renal cell carcinoma, NSCLC, and hepatocellular carcinoma, resulting in approval of the ipilimumab and nivolumab (anti–PD-1) combination for their treatment (20, 35, 42, 43).