Unbiased analysis of all possible neoepitopes of MC38-FABF tumor reveals a new universe of cancer neoepitopes with unexpected properties

Abstract

Cancer neoepitopes are the only truly tumor-specific antigens and therefore, the most suitable as cancer vaccines. Current methods to predict neoepitopes, based on studies of viral epitopes, emphasize high affinity MHC-peptide interactions. Increasing evidence in human and murine models indicates that the present neoepitope prediction methods are mostly inaccurate in predicting true MHC I-restricted cancer neoepitopes. Here, in a completely unbiased approach, all possible neoepitopes in a mouse tumor model were tested for their ability to mediate tumor rejection and also CD8⁺ T cell responses. These studies show that the true tumor rejecting neoepitopes have different properties from those of viral epitopes. Further, CD8⁺ T cell responses elicited by these neoepitopes possess a more plastic chromatin phenotype with stem-like properties that is known to be associated with anti-viral and anti-tumor immune responses. Such cancer neoepitopes can be exploited for generation of personalized cancer vaccines.