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@ARTICLE{Velz:298571,
author = {J. Velz and L. Freudenmann$^*$ and G. Medici and M.
Dubbelaar and M. Mohme and D. R. Ghasemi$^*$ and J. Scheid
and D. J. Kowalewski and A. B. Patterson and A. M.
Zeitlberger and K. Lamszus and M. Westphal and M. Eyrich and
M. Messing-Jünger and A. Röhrig and H. Reinhard and K.
Beccaria and R. B. Craveiro and B. M. Frey and M. Sill$^*$
and S. Nahnsen and M. Gauder and K. Kapolou and M. Silginer
and T. Weiss and H.-G. Wirsching and P. Roth and M. Grotzer
and N. Krayenbühl and O. Bozinov and L. Regli and H.-G.
Rammensee$^*$ and E. J. Rushing and F. Sahm$^*$ and J.
Walz$^*$ and M. Weller and M. C. Neidert},
title = {{M}apping naturally presented {T} cell antigens in
medulloblastoma based on integrative multi-omics.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-00288},
pages = {1364},
year = {2025},
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.},
keywords = {Medulloblastoma: immunology / Medulloblastoma: genetics /
Humans / Cerebellar Neoplasms: immunology / Cerebellar
Neoplasms: genetics / Antigens, Neoplasm: immunology /
Antigens, Neoplasm: genetics / Child / T-Lymphocytes:
immunology / Antigen Presentation: immunology /
Histocompatibility Antigens Class I: immunology /
Histocompatibility Antigens Class I: genetics / Male /
Female / Peptides: immunology / HLA Antigens: genetics / HLA
Antigens: immunology / Proteomics / Immunotherapy: methods /
Multiomics / Antigens, Neoplasm (NLM Chemicals) /
Histocompatibility Antigens Class I (NLM Chemicals) /
Peptides (NLM Chemicals) / HLA Antigens (NLM Chemicals)},
cin = {TU01 / B062 / HD01 / B300},
ddc = {500},
cid = {I:(DE-He78)TU01-20160331 / I:(DE-He78)B062-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)B300-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39904979},
doi = {10.1038/s41467-025-56268-0},
url = {https://inrepo02.dkfz.de/record/298571},
}