Presented by Ms. Andrea Castro, PhD Student, University of California at San Diego Cancer is a heterogenous disease, largely initiated and driven by genomic alterations. Some of these alterations can be detected by immune surveillance, leading the adaptive immune system to attack tumor cells. Indeed, immune evasion is one of the hallmark behaviors shared by all cancers. The major histocompatibility complexes (MHC) are central to immune surveillance, determining which of the genomic alterations in tumor cells can be presented to T cells. The peptide binding region of MHC-I is encoded by the highly polymorphic HLA genes (HLA-A/B/C) which ultimately determine peptide-MHC specificities. Tumor cells with "invisible" mutations escape immune surveillance whereas cells with "visible" mutations are more likely to be recognized and eliminated by T cells. Several studies have found that tumor genome landscapes show a bias for mutations that are "invisible" to the MHC. To better understand the factors that influence host anti-tumor immunity, we studied tumor mutation landscapes in the TCGA and found that mutation landscapes from tumors occurring in younger and female individuals are more depleted of "visible" mutations, suggesting that a stronger immune system may produce stronger constraints on tumor evolution. Furthermore, loss of integrity of the MHC is reflected by an excess of well-presented mutations. These findings have implications for developing effective immunotherapies.