The basis of these clinical trials comes from several decades of fundamental research in experimental mouse models that have revealed the importance of CTLA‐4 and PD‐1 in restraining immune responses, as most clearly illustrated by the severe spontaneous autoimmunity phenotype in CTLA‐4‐deficient (Waterhouse et al, 1995) and to a milder extent in PD‐1‐deficient mice (Nishimura et al, 1999, 2001). This evidence concerns the gene CTLA4 and Autoimmunity.