Traditionally viewed as checkpoint inhibitors, anti-CTLA-4 antibodies have been postulated to achieve immunotherapy by antagonizing the endogenous function of CTLA-4.27,28 Since genetic inactivation of CTLA-4 in mice and humans has caused severe autoimmune diseases,5–7 an effective antagonist of CTLA-4 molecule is likely to induce autoimmune diseases, making irAE a necessary price for cancer immunity. This evidence concerns the gene CTLA4 and cancer.