Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification
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Published:2023-08-02
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Tretter CelinaORCID, de Andrade Krätzig NiklasORCID, Pecoraro Matteo, Lange SebastianORCID, Seifert Philipp, von Frankenberg Clara, Untch JohannesORCID, Zuleger GabrielaORCID, Wilhelm MathiasORCID, Zolg Daniel P., Dreyer Florian S., Bräunlein Eva, Engleitner Thomas, Uhrig Sebastian, Boxberg Melanie, Steiger KatjaORCID, Slotta-Huspenina Julia, Ochsenreither SebastianORCID, von Bubnoff Nikolas, Bauer SebastianORCID, Boerries MelanieORCID, Jost Philipp J., Schenck Kristina, Dresing Iska, Bassermann FlorianORCID, Friess Helmut, Reim DanielORCID, Grützmann Konrad, Pfütze Katrin, Klink BarbaraORCID, Schröck EvelinORCID, Haller BernhardORCID, Kuster BernhardORCID, Mann MatthiasORCID, Weichert Wilko, Fröhling StefanORCID, Rad RolandORCID, Hiltensperger MichaelORCID, Krackhardt Angela M.ORCID
Abstract
AbstractSystemic pan-tumor analyses may reveal the significance of common features implicated in cancer immunogenicity and patient survival. Here, we provide a comprehensive multi-omics data set for 32 patients across 25 tumor types for proteogenomic-based discovery of neoantigens. By using an optimized computational approach, we discover a large number of tumor-specific and tumor-associated antigens. To create a pipeline for the identification of neoantigens in our cohort, we combine DNA and RNA sequencing with MS-based immunopeptidomics of tumor specimens, followed by the assessment of their immunogenicity and an in-depth validation process. We detect a broad variety of non-canonical HLA-binding peptides in the majority of patients demonstrating partially immunogenicity. Our validation process allows for the selection of 32 potential neoantigen candidates. The majority of neoantigen candidates originates from variants identified in the RNA data set, illustrating the relevance of RNA as a still understudied source of cancer antigens. This study underlines the importance of RNA-centered variant detection for the identification of shared biomarkers and potentially relevant neoantigen candidates.
Funder
Deutsches Krebsforschungszentrum
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
17 articles.
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