Journal Article

DKFZ-2025-00288

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics.

Velz, J. ; Freudenmann, L.DKFZ* ; Medici, G. ; Dubbelaar, M. ; Mohme, M. ; Ghasemi, D. R.DKFZ* ; Scheid, J. ; Kowalewski, D. J. ; Patterson, A. B. ; Zeitlberger, A. M. ; Lamszus, K. ; Westphal, M. ; Eyrich, M. ; Messing-Jünger, M. ; Röhrig, A. ; Reinhard, H. ; Beccaria, K. ; Craveiro, R. B. ; Frey, B. M. ; Sill, M.DKFZ* ; Nahnsen, S. ; Gauder, M. ; Kapolou, K. ; Silginer, M. ; Weiss, T. ; Wirsching, H.-G. ; Roth, P. ; Grotzer, M. ; Krayenbühl, N. ; Bozinov, O. ; Regli, L. ; Rammensee, H.-G.DKFZ* ; Rushing, E. J. ; Sahm, F.DKFZ* ; Walz, J.DKFZ* ; Weller, M. ; Neidert, M. C.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s41467-025-56268-0

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.

Keyword(s): Medulloblastoma: immunology (MeSH) ; Medulloblastoma: genetics (MeSH) ; Humans (MeSH) ; Cerebellar Neoplasms: immunology (MeSH) ; Cerebellar Neoplasms: genetics (MeSH) ; Antigens, Neoplasm: immunology (MeSH) ; Antigens, Neoplasm: genetics (MeSH) ; Child (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Antigen Presentation: immunology (MeSH) ; Histocompatibility Antigens Class I: immunology (MeSH) ; Histocompatibility Antigens Class I: genetics (MeSH) ; Male (MeSH) ; Female (MeSH) ; Peptides: immunology (MeSH) ; HLA Antigens: genetics (MeSH) ; HLA Antigens: immunology (MeSH) ; Proteomics (MeSH) ; Immunotherapy: methods (MeSH) ; Multiomics (MeSH) ; Antigens, Neoplasm ; Histocompatibility Antigens Class I ; Peptides ; HLA Antigens

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Tübingen (TU01)
2. B062 Pädiatrische Neuroonkologie (B062)
3. DKTK HD zentral (HD01)
4. KKE Neuropathologie (B300)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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