TY  - JOUR
AU  - Velz, Julia
AU  - Freudenmann, Lena
AU  - Medici, Gioele
AU  - Dubbelaar, Marissa
AU  - Mohme, Malte
AU  - Ghasemi, David R
AU  - Scheid, Jonas
AU  - Kowalewski, Daniel J
AU  - Patterson, Angelica B
AU  - Zeitlberger, Anna M
AU  - Lamszus, Katrin
AU  - Westphal, Manfred
AU  - Eyrich, Matthias
AU  - Messing-Jünger, Martina
AU  - Röhrig, Andreas
AU  - Reinhard, Harald
AU  - Beccaria, Kévin
AU  - Craveiro, Rogeiro B
AU  - Frey, Beat M
AU  - Sill, Martin
AU  - Nahnsen, Sven
AU  - Gauder, Marie
AU  - Kapolou, Konstantina
AU  - Silginer, Manuela
AU  - Weiss, Tobias
AU  - Wirsching, Hans-Georg
AU  - Roth, Patrick
AU  - Grotzer, Michael
AU  - Krayenbühl, Niklaus
AU  - Bozinov, Oliver
AU  - Regli, Luca
AU  - Rammensee, Hans-Georg
AU  - Rushing, Elisabeth J
AU  - Sahm, Felix
AU  - Walz, Juliane
AU  - Weller, Michael
AU  - Neidert, Marian C
TI  - Mapping naturally presented T cell antigens in medulloblastoma based on integrative multi-omics.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-00288
SP  - 1364
PY  - 2025
AB  - 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.
KW  - Medulloblastoma: immunology
KW  - Medulloblastoma: genetics
KW  - Humans
KW  - Cerebellar Neoplasms: immunology
KW  - Cerebellar Neoplasms: genetics
KW  - Antigens, Neoplasm: immunology
KW  - Antigens, Neoplasm: genetics
KW  - Child
KW  - T-Lymphocytes: immunology
KW  - Antigen Presentation: immunology
KW  - Histocompatibility Antigens Class I: immunology
KW  - Histocompatibility Antigens Class I: genetics
KW  - Male
KW  - Female
KW  - Peptides: immunology
KW  - HLA Antigens: genetics
KW  - HLA Antigens: immunology
KW  - Proteomics
KW  - Immunotherapy: methods
KW  - Multiomics
KW  - Antigens, Neoplasm (NLM Chemicals)
KW  - Histocompatibility Antigens Class I (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - HLA Antigens (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39904979
DO  - DOI:10.1038/s41467-025-56268-0
UR  - https://inrepo02.dkfz.de/record/298571
ER  -