%0 Journal Article
%A Velz, Julia
%A Freudenmann, Lena
%A Medici, Gioele
%A Dubbelaar, Marissa
%A Mohme, Malte
%A Ghasemi, David R
%A Scheid, Jonas
%A Kowalewski, Daniel J
%A Patterson, Angelica B
%A Zeitlberger, Anna M
%A Lamszus, Katrin
%A Westphal, Manfred
%A Eyrich, Matthias
%A Messing-Jünger, Martina
%A Röhrig, Andreas
%A Reinhard, Harald
%A Beccaria, Kévin
%A Craveiro, Rogeiro B
%A Frey, Beat M
%A Sill, Martin
%A Nahnsen, Sven
%A Gauder, Marie
%A Kapolou, Konstantina
%A Silginer, Manuela
%A Weiss, Tobias
%A Wirsching, Hans-Georg
%A Roth, Patrick
%A Grotzer, Michael
%A Krayenbühl, Niklaus
%A Bozinov, Oliver
%A Regli, Luca
%A Rammensee, Hans-Georg
%A Rushing, Elisabeth J
%A Sahm, Felix
%A Walz, Juliane
%A Weller, Michael
%A Neidert, Marian C
%T Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics.
%J Nature Communications
%V 16
%N 1
%@ 2041-1723
%C [London]
%I Springer Nature
%M DKFZ-2025-00288
%P 1364
%D 2025
%X 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.
%K Medulloblastoma: immunology
%K Medulloblastoma: genetics
%K Humans
%K Cerebellar Neoplasms: immunology
%K Cerebellar Neoplasms: genetics
%K Antigens, Neoplasm: immunology
%K Antigens, Neoplasm: genetics
%K Child
%K T-Lymphocytes: immunology
%K Antigen Presentation: immunology
%K Histocompatibility Antigens Class I: immunology
%K Histocompatibility Antigens Class I: genetics
%K Male
%K Female
%K Peptides: immunology
%K HLA Antigens: genetics
%K HLA Antigens: immunology
%K Proteomics
%K Immunotherapy: methods
%K Multiomics
%K Antigens, Neoplasm (NLM Chemicals)
%K Histocompatibility Antigens Class I (NLM Chemicals)
%K Peptides (NLM Chemicals)
%K HLA Antigens (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39904979
%R 10.1038/s41467-025-56268-0
%U https://inrepo02.dkfz.de/record/298571