PDCD1 and metastatic melanoma: For example, the combination of ipilimumab (anti-CTLA-4) plus nivolumab (anti-PD-1) was shown to significantly enhance efficacy in patients with metastatic melanoma; therefore, ipilimumab plus nivolumab was approved for the treatment of metastatic melanoma, advanced renal cell carcinoma, and metastatic colorectal cancer (14).