Since 2011, several immune checkpoint inhibitors have been approved by the US FDA for second- and even first-line treatment against various cancer types, such as lung cancer, renal cell carcinoma, bladder cancer, gastric cancer, and many others; these include the CTLA-4–blocking antibody ipilimumab (5), three antibodies against Programmed Cell Death Receptor-1 (PD-1, CD279) [pembrolizumab (6), nivolumab (7), and cemiplimab (8)], and three antibodies targeting Programmed Cell Death Ligand-1 (PD-L1, CD274) [atezolizumab (9), avelumab (10), and durvalumab (11)]. The gene discussed is CD274; the disease is hereditary clear cell renal cell carcinoma.