Proteogenomic analysis reveals RNA as a source for tumor-agnostic neoantigen identification.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 08 2023
Historique:
received: 27 09 2022
accepted: 19 06 2023
medline: 4 8 2023
pubmed: 3 8 2023
entrez: 2 8 2023
Statut: epublish

Résumé

Systemic 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.

Identifiants

pubmed: 37532709
doi: 10.1038/s41467-023-39570-7
pii: 10.1038/s41467-023-39570-7
pmc: PMC10397250
doi:

Substances chimiques

Antigens, Neoplasm 0
Peptides 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4632

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s).

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Auteurs

Celina Tretter (C)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Niklas de Andrade Krätzig (N)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department, Munich, Germany.
Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.
Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics, Munich, Germany.

Matteo Pecoraro (M)

Department of Proteomics and Signal Transduction, Max Plank Institute of Biochemistry, Munich, Germany.
Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland.

Sebastian Lange (S)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department, Munich, Germany.
Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.
Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics, Munich, Germany.

Philipp Seifert (P)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Clara von Frankenberg (C)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Johannes Untch (J)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Gabriela Zuleger (G)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Mathias Wilhelm (M)

Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics, Freising, Germany.
Technical University of Munich, TUM School of Life Sciences, Computational Mass Spectrometry, Freising, Germany.

Daniel P Zolg (DP)

Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics, Freising, Germany.

Florian S Dreyer (FS)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Eva Bräunlein (E)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Thomas Engleitner (T)

Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.
Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics, Munich, Germany.

Sebastian Uhrig (S)

German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Molecular Precision Oncology Program, NCT Heidelberg, Heidelberg, Germany.

Melanie Boxberg (M)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology, Munich, Germany.

Katja Steiger (K)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology, Munich, Germany.

Julia Slotta-Huspenina (J)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology, Munich, Germany.

Sebastian Ochsenreither (S)

German Cancer Consortium (DKTK), partner site Berlin and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Charité Comprehensive Cancer Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Hematology, Oncology and Tumor Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Nikolas von Bubnoff (N)

German Cancer Consortium (DKTK), partner site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Medical Bioinformatics and Systems Medicine (IBSM), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Department of Hematology and Oncology, Medical Center, University of Schleswig Holstein, Campus Lübeck, Lübeck, Germany.

Sebastian Bauer (S)

German Cancer Consortium (DKTK), partner site Essen and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Department of Medical Oncology and Sarcoma Center, West German Cancer Center, University Hospital Essen, Essen, Germany.

Melanie Boerries (M)

German Cancer Consortium (DKTK), partner site Freiburg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Medical Bioinformatics and Systems Medicine (IBSM), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Philipp J Jost (PJ)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.
Clinical Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
University Comprehensive Cancer Center Graz, Medical University of Graz, Graz, Austria.

Kristina Schenck (K)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Iska Dresing (I)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Florian Bassermann (F)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.
Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.

Helmut Friess (H)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Department of Surgery, Munich, Germany.

Daniel Reim (D)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Department of Surgery, Munich, Germany.

Konrad Grützmann (K)

German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Core Unit Molecular Tumor Diagnostics (CMTD), NCT Dresden, Dresden, Germany.
Institute for Medical Informatics and Biometry, Faculty of Medicine, TU Dresden, Dresden, Germany.

Katrin Pfütze (K)

German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.

Barbara Klink (B)

German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.

Evelin Schröck (E)

German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute for Clinical Genetics, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany.
ERN GENTURIS, Hereditary Cancer Syndrome Center Dresden, Dresden, Germany.
National Center for Tumor Diseases Dresden (NCT/UCC), Dresden, Germany.
Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Dresden, Germany.
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.

Bernhard Haller (B)

Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of AI and Informatics in Medicine, Munich, Germany.

Bernhard Kuster (B)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Life Sciences, Chair of Proteomics and Bioanalytics, Freising, Germany.
Technical University of Munich, TUM School of Life Sciences, Bavarian Biomolecular Mass Spectrometry Center (BayBioMS), Freising, Germany.

Matthias Mann (M)

Department of Proteomics and Signal Transduction, Max Plank Institute of Biochemistry, Munich, Germany.

Wilko Weichert (W)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, Institute of Pathology, Munich, Germany.

Stefan Fröhling (S)

German Cancer Consortium (DKTK), partner site Heidelberg and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Division of Translational Medical Oncology, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Roland Rad (R)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IInd Medical Department, Munich, Germany.
Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany.
Technical University of Munich, TUM School of Medicine, Institute of Molecular Oncology and Functional Genomics, Munich, Germany.

Michael Hiltensperger (M)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany.

Angela M Krackhardt (AM)

German Cancer Consortium (DKTK), partner site Munich and German Cancer Research Center (DKFZ), Heidelberg, Germany. angela.krackhardt@tum.de.
Technical University of Munich, TUM School of Medicine, Klinikum rechts der Isar, IIIrd Medical Department, Munich, Germany. angela.krackhardt@tum.de.
Technical University of Munich, TUM School of Medicine, Center for Translational Cancer Research (TranslaTUM), Munich, Germany. angela.krackhardt@tum.de.
Malteser Krankenhaus St. Franziskus-Hospital, Flensburg, Germany. angela.krackhardt@tum.de.

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