The traditional concept of checkpoint blockade stipulates that anti-CTLA-4 antibodies promote tumor immunity by antagonizing a physiological checkpoint against autoimmunity.27,28 Given the fact that homozygous or heterozygous inactivation of the CTLA4 gene5–7 or another gene involved in CTLA-4 recycling causes autoimmune diseases,36 effective antagonism of endogenous CTLA-4 function will necessarily increase the risk of autoimmune diseases. The gene discussed is CTLA4; the disease is Autoimmunity.