After the approval of ipilimumab (targeting CTLA-4) and pembrolizumab and nivolumab (targeting PD-1) for the treatment of metastatic melanoma, the clinical benefit of immune checkpoint blockers (ICBs) have been quickly appreciated for a growing number of cancer types, including non-small cell lung cancer, microsatellite instability-high (MSI-H) CRC, gastric cancer, Hodgkin lymphoma, head and neck squamous cell, hepatocellular, renal cancer, Merkel cell, and urothelial carcinoma [35]. This evidence concerns the gene CTLA4 and cancer.