Mining the Immunopeptidome for Antigenic Peptides in Cancer

SIMPLE SUMMARY: The immunopeptidome of cancer cells is a treasure trove of neoantigens bound to MHC molecules, thus a great source for mining immunopeptides for immunotherapy applications, including cancer vaccines. Immunopeptides may encompass post-translational modifications that are overlooked by genomic and transcriptomic tools. We review post-translational modifications that have been uncovered, and how this information could be harnessed for cancer vaccines. ABSTRACT: Although harnessing the immune system for cancer therapy has shown success, response to immunotherapy has been limited. The immunopeptidome of cancer cells presents an opportunity to discover novel antigens for immunotherapy applications. These neoantigens bind to MHC class I and class II molecules. Remarkably, the immunopeptidome encompasses protein post-translation modifications (PTMs) that may not be evident from genome or transcriptome profiling. A case in point is citrullination, which has been demonstrated to induce a strong immune response. In this review, we cover how the immunopeptidome, with a special focus on PTMs, can be utilized to identify cancer-specific antigens for immunotherapeutic applications.