Effector T cell responses directed toward cancer neoantigens mediate tumor regression following checkpoint blockade or adoptive T cell immunotherapy, but are generally “private”, thus requiring considerable effort for their identification. In this issue of the JCI, Malekzadeh et al. show that a fraction of patients with epithelial cancers mount antigen-specific T cell responses to “hot spot” p53 mutations that in some cases are shared among patients. This work suggests that other genes frequently mutated in human cancer can be immunogenic, thus offering a rapid way to screen for cancer neoantigens that can be targeted by subsequent T cell–based therapies.