TOF IMS mass spectrometry-based immunopeptidomics refines tumor antigen identification.

Autor: Hoenisch Gravel N; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Nelde A; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Bauer J; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Mühlenbruch L; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany., Schroeder SM; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Otorhinolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany., Neidert MC; Neuroscience Center Zürich (ZNZ), University of Zürich and ETH Zürich, Zürich, Switzerland.; Clinical Neuroscience Center and Department of Neurosurgery, University Hospital and University of Zurich, Zürich, Switzerland.; Department of Neurosurgery, Cantonal Hospital St. Gallen, Zürich, Switzerland., Scheid J; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Quantitative Biology Center (QBIC), University of Tübingen, Tübingen, Germany., Lemke S; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Quantitative Biology Center (QBIC), University of Tübingen, Tübingen, Germany., Dubbelaar ML; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Quantitative Biology Center (QBIC), University of Tübingen, Tübingen, Germany., Wacker M; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Dengler A; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Klein R; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany., Mauz PS; Department of Otorhinolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany., Löwenheim H; Department of Otorhinolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany., Hauri-Hohl M; Pediatric Stem Cell Transplantation, University Children's Hospital Zürich, Zürich, Switzerland., Martin R; Neuroimmunology and MS Research, Neurology Clinic, University and University Hospital Zürich, Zürich, Switzerland., Hennenlotter J; Department of Urology, University Hospital Tübingen, Tübingen, Germany., Stenzl A; Department of Urology, University Hospital Tübingen, Tübingen, Germany., Heitmann JS; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Salih HR; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Rammensee HG; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), partner site Tübingen, Tübingen, Germany., Walz JS; Department of Peptide-based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany. juliane.walz@med.uni-tuebingen.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Nov 17; Vol. 14 (1), pp. 7472. Date of Electronic Publication: 2023 Nov 17.
DOI: 10.1038/s41467-023-42692-7
Abstrakt: T cell recognition of human leukocyte antigen (HLA)-presented tumor-associated peptides is central for cancer immune surveillance. Mass spectrometry (MS)-based immunopeptidomics represents the only unbiased method for the direct identification and characterization of naturally presented tumor-associated peptides, a key prerequisite for the development of T cell-based immunotherapies. This study reports on the implementation of ion mobility separation-based time-of-flight (TOF IMS ) MS for next-generation immunopeptidomics, enabling high-speed and sensitive detection of HLA-presented peptides. Applying TOF IMS -based immunopeptidomics, a novel extensive benign TOFIMS dataset was generated from 94 primary benign samples of solid tissue and hematological origin, which enabled the expansion of benign reference immunopeptidome databases with > 150,000 HLA-presented peptides, the refinement of previously described tumor antigens, as well as the identification of frequently presented self antigens and not yet described tumor antigens comprising low abundant mutation-derived neoepitopes that might serve as targets for future cancer immunotherapy development.
(© 2023. The Author(s).)
Databáze: MEDLINE
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