Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics
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 o...
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2025-02-01
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| author | Julia Velz Lena K. Freudenmann Gioele Medici Marissa Dubbelaar Malte Mohme David R. Ghasemi Jonas Scheid Daniel J. Kowalewski Angelica B. Patterson Anna M. Zeitlberger Katrin Lamszus Manfred Westphal Matthias Eyrich Martina Messing-Jünger Andreas Röhrig Harald Reinhard Kévin Beccaria Rogeiro B. Craveiro Beat M. Frey Martin Sill Sven Nahnsen Marie Gauder Konstantina Kapolou Manuela Silginer Tobias Weiss Hans-Georg Wirsching Patrick Roth Michael Grotzer Niklaus Krayenbühl Oliver Bozinov Luca Regli Hans-Georg Rammensee Elisabeth J. Rushing Felix Sahm Juliane S. Walz Michael Weller Marian C. Neidert |
| author_facet | Julia Velz Lena K. Freudenmann Gioele Medici Marissa Dubbelaar Malte Mohme David R. Ghasemi Jonas Scheid Daniel J. Kowalewski Angelica B. Patterson Anna M. Zeitlberger Katrin Lamszus Manfred Westphal Matthias Eyrich Martina Messing-Jünger Andreas Röhrig Harald Reinhard Kévin Beccaria Rogeiro B. Craveiro Beat M. Frey Martin Sill Sven Nahnsen Marie Gauder Konstantina Kapolou Manuela Silginer Tobias Weiss Hans-Georg Wirsching Patrick Roth Michael Grotzer Niklaus Krayenbühl Oliver Bozinov Luca Regli Hans-Georg Rammensee Elisabeth J. Rushing Felix Sahm Juliane S. Walz Michael Weller Marian C. Neidert |
| author_sort | Julia Velz |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b9fe273a58d54ecda74c0989948827ea |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
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| spelling | doaj-art-b9fe273a58d54ecda74c0989948827ea2025-02-09T12:44:02ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-56268-0Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omicsJulia Velz0Lena K. Freudenmann1Gioele Medici2Marissa Dubbelaar3Malte Mohme4David R. Ghasemi5Jonas Scheid6Daniel J. Kowalewski7Angelica B. Patterson8Anna M. Zeitlberger9Katrin Lamszus10Manfred Westphal11Matthias Eyrich12Martina Messing-Jünger13Andreas Röhrig14Harald Reinhard15Kévin Beccaria16Rogeiro B. Craveiro17Beat M. Frey18Martin Sill19Sven Nahnsen20Marie Gauder21Konstantina Kapolou22Manuela Silginer23Tobias Weiss24Hans-Georg Wirsching25Patrick Roth26Michael Grotzer27Niklaus Krayenbühl28Oliver Bozinov29Luca Regli30Hans-Georg Rammensee31Elisabeth J. Rushing32Felix Sahm33Juliane S. Walz34Michael Weller35Marian C. Neidert36Laboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichInstitute of Immunology, University of TübingenLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichDepartment of Peptide-based Immunotherapy, Institute of Immunology, University and University Hospital TübingenDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK)Institute of Immunology, University of TübingenInstitute of Immunology, University of TübingenInstitute of Immunobiology, Cantonal Hospital St.GallenDepartment of Neurosurgery, Cantonal Hospital St.GallenDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDepartment of Neurosurgery, University Medical Center Hamburg-EppendorfDepartment of Pediatric Haematology, Oncology and Stem Cell Transplantation, University Children’s Hospital, University Medical Center, University of WürzburgDepartment of Neurosurgery, Asklepios Children’s HospitalDepartment of Neurosurgery, Asklepios Children’s HospitalDepartment of Pediatrics, Asklepios Children’s HospitalDepartment of Pediatric Neurosurgery, Necker Enfants Malades Hospital, APHP, Université Paris CiteDepartment of Orthodontic, Dental Clinic, University Hospital of RWTH AachenBlood Transfusion Service, Swiss Red CrossDivision of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Consortium for Translational Cancer Research (DKTK)Quantitative Biology Center (QBiC), University of TübingenQuantitative Biology Center (QBiC), University of TübingenLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichDepartment of Oncology, University Children’s Hospital ZürichDepartment of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of ZurichDepartment of Neurosurgery, Cantonal Hospital St.GallenDepartment of Neurosurgery, Clinical Neuroscience Center, University Hospital and University of ZurichInstitute of Immunology, University of TübingenDepartment of Neuropathology, University Hospital and University of ZurichDepartment of Neuropathology, Heidelberg University Hospital, and CCU Neuropathology, German Consortium for Translational Cancer Research (DKTK), German Cancer Research Center (DKFZ)German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Partner Site TübingenLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichLaboratory of Molecular Neuro-Oncology, Department of Neurology, Clinical Neuroscience Center, University Hospital and University of ZurichAbstract 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.https://doi.org/10.1038/s41467-025-56268-0 |
| spellingShingle | Julia Velz Lena K. Freudenmann Gioele Medici Marissa Dubbelaar Malte Mohme David R. Ghasemi Jonas Scheid Daniel J. Kowalewski Angelica B. Patterson Anna M. Zeitlberger Katrin Lamszus Manfred Westphal Matthias Eyrich Martina Messing-Jünger Andreas Röhrig Harald Reinhard Kévin Beccaria Rogeiro B. Craveiro Beat M. Frey Martin Sill Sven Nahnsen Marie Gauder Konstantina Kapolou Manuela Silginer Tobias Weiss Hans-Georg Wirsching Patrick Roth Michael Grotzer Niklaus Krayenbühl Oliver Bozinov Luca Regli Hans-Georg Rammensee Elisabeth J. Rushing Felix Sahm Juliane S. Walz Michael Weller Marian C. Neidert Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics Nature Communications |
| title | Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics |
| title_full | Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics |
| title_fullStr | Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics |
| title_full_unstemmed | Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics |
| title_short | Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics |
| title_sort | mapping naturally presented t cell antigens in medulloblastoma based on integrative multi omics |
| url | https://doi.org/10.1038/s41467-025-56268-0 |
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