Whereas blocking antibodies against PD-1, PD-L1, and CTLA-4, known as immune checkpoint inhibitors, have exhibited clinical efficacy in deficient mismatch repair (MMR) or in highly microsatellite instable (MSI-H) colorectal cancer, the vast majority of patients with proficient MMR and with microsatellite stable (MSS) tumors do not benefit from immunotherapy (46–48). The gene discussed is CTLA4; the disease is colorectal cancer.