Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics

Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T cell antigens in medulloblastoma. We map the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and perform comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma is shown to be a rich source of tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins are subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) is rare. Functional testing of top-ranking novel candidate antigens demonstrates the induction of peptide-specific T cell responses, supporting their potential for T cell immunotherapy. This study is an in-depth mapping of naturally presented T cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data leads to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.

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Publication Details

Journal
Nature Communications
Published
2025-02-04
DOI
https://doi.org/10.1038/s41467-025-56268-0
Citations
4
Primary Topic
Immunotherapy and Immune Responses
Type
article
Field-Weighted Citation Impact
3.19

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article

Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics

Manuela Silginer, Andreas Röhrig, Martina Messing‐Jünger, Sven Nahnsen et al.
4 citations
Nature Communications
Immunotherapy and Immune Responses
3.19
article

Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics

Manuela Silginer, Andreas Röhrig, Martina Messing‐Jünger, Sven Nahnsen, Marie Gauder, Tobias Weiß, Michael Weller, Katrin Lamszus, Michael A. Grotzer, Harald Reinhard, Matthias Eyrich, David R. Ghasemi, Beat M. Frey, Anna Maria Zeitlberger, Kévin Beccaria, Patrick Roth, Lena Katharina Freudenmann, Konstantina Kapolou, Marian Christoph Neidert, Marissa L. Dubbelaar, Oliver Bozinov, Julia Velz, Luca Regli, Felix Sahm, Malte Mohme, Manfred Westphal, Angelica B Patterson, Jonas Scheid, Gioele Medici, Elisabeth J. Rushing, Juliane S. Walz, Daniel J. Kowalewski, Hans‐Georg Rammensee, Hans‐Georg Wirsching, Martin Sill, Niklaus Krayenbuehl, Rogeiro B Craveiro
article en
4 citations

Abstract

Medulloblastoma is the most frequent malignant primary brain tumor in children. Despite recent advances in integrated genomics, the prognosis in children with high-risk medulloblastoma remains devastating, and new tumor-specific therapeutic approaches are needed. Here, we present an atlas of naturally presented T cell antigens in medulloblastoma. We map the human leukocyte antigen (HLA)-presented peptidomes of 28 tumors and perform comparative immunopeptidome profiling against an in-house benign database. Medulloblastoma is shown to be a rich source of tumor-associated antigens, naturally presented on HLA class I and II molecules. Remarkably, most tumor-associated peptides and proteins are subgroup-specific, whereas shared presentation among all subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) is rare. Functional testing of top-ranking novel candidate antigens demonstrates the induction of peptide-specific T cell responses, supporting their potential for T cell immunotherapy. This study is an in-depth mapping of naturally presented T cell antigens in medulloblastoma. Integration of immunopeptidomics, transcriptomics, and epigenetic data leads to the identification of a large set of actionable targets that can be further used for the translation into the clinical setting by facilitating the informed design of immunotherapeutic approaches to children with medulloblastoma.

Nature CommunicationsVol. 16(1)
Universität Hamburg (DE), German Cancer Research Center (DE), Swiss Red Cross (CH), University of Zurich (CH), University of St.Gallen (CH), Université Paris Cité (FR), Heidelberg University (DE), University of Würzburg (DE), University Hospital Heidelberg (DE), Assistance Publique – Hôpitaux de Paris (FR), University Hospital of Zurich (CH), University Medical Center Hamburg-Eppendorf (DE), Kinderkrebs-Zentrum Hamburg (DE), Hopp Children's Cancer Center Heidelberg (DE), University Children's Hospital Tübingen (DE), Universitätsklinikum Würzburg (DE), Asklepios Klinik Sankt Augustin (DE), University Children's Hospital Zurich (CH), Bernstein Center for Computational Neuroscience Tübingen (DE), Deutsches Konsortium für Translationale Krebsforschung (DE), University of Tübingen (DE), RWTH Aachen University (DE)
Deutsche Forschungsgemeinschaft, Studienstiftung des Deutschen Volkes, Universität Zürich, Deutschen Konsortium für Translationale Krebsforschung
Zero hunger
Openalex Percentile: Top 9%
Immunotherapy and Immune Responses
3.19
DOIOpen Access PDFOpenAlex
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