Under physiological conditions, immune checkpoints are critical for maintaining self-tolerance and preventing the development of autoimmunity; however, in the setting of cancer and chronic infections, the persistence of antigen can lead to T cell exhaustion, a dysfunctional state with impaired effector function and cytotoxicity and upregulation of inhibitory molecules such as PD-1 and CTLA-4.14,15 ICIs block the receptor–ligand interactions of these inhibitory molecules, resulting in a rejuvenation of the immune response and a more robust anti-tumoral or anti-infectious response. The gene discussed is CTLA4; the disease is cancer.