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- W3154181570 abstract "Abstract Antigen processing and presentation are critical for modulating tumor-host interactions. While post-translational modifications (PTMs) can alter the binding and recognition of antigens, their identification remains challenging. Here we uncover the role PTMs may play in antigen presentation and recognition in human cancers by profiling 29 different PTM combinations in immunopeptidomics data from multiple clinical samples and cell lines. We established and validated an antigen discovery pipeline and showed that newly identified modified antigens from a murine cancer model are cancer-specific and can elicit T cell killing. Systematic analysis of PTMs across multiple cohorts defined new haplotype preferences and binding motifs in association with specific PTM types. By expanding the antigenic landscape with modifications, we uncover disease-specific targets, including thousands of novel cancer-specific antigens and reveal insight into PTM-driven antigenicity. Collectively, our findings highlight an immunomodulatory role for modified peptides presented on HLA I, which may have broad implications for T-cell mediated therapies in cancer and beyond. Significance Major efforts are underway to identify cancer-specific antigens for personalized immunotherapy. Here, we enrich the immunopeptidome landscape by uncovering thousands of novel putative antigens that are post-translationally modified. We define unique preferences for PTM-driven alterations affecting HLA binding and TCR recognition, which in turn alter tumor-immune interactions. Conflict of interest statement Authors declare no conflicts of interest." @default.
- W3154181570 created "2021-04-26" @default.
- W3154181570 creator A5001176337 @default.
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- W3154181570 date "2021-04-11" @default.
- W3154181570 modified "2023-10-16" @default.
- W3154181570 title "Uncovering the modified immunopeptidome reveals insights into principles of PTM-driven antigenicity" @default.
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