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@ARTICLE{Mhlenbruch:301479,
author = {L. Mühlenbruch and D. Rieger and H. Becker and A. M.
Santos Leite and I. Mäurer and J. Schittenhelm$^*$ and M.
Dubbelaar and L. Bichmann and O. Kohlbacher and H.-G.
Rammensee$^*$ and C. Gouttefangeas$^*$ and M. Tatagiba$^*$
and J. Walz$^*$ and G. Tabatabai$^*$},
title = {{T}he immunopeptidomic landscape of ependymomas provides
actionable antigens for {T}-cell-based immunotherapy.},
journal = {Neuro-oncology advances},
volume = {7},
number = {1},
issn = {2632-2498},
address = {Oxford},
publisher = {Oxford University Press},
reportid = {DKFZ-2025-01021},
pages = {vdae226},
year = {2025},
abstract = {Ependymoma are primary tumors of the nervous system. Due to
their growth pattern, many ependymomas can be managed with
neurosurgical resection alone. A substantial proportion of
these tumors recurs or displays infiltrative growth
patterns. Further established therapeutic options include
radiation therapy. Systemic treatment options include
platinum-based therapeutic regimes or a combination of
lapatinib and temozolomide. Peptide-based immunotherapy
represents a promising therapeutic strategy relying on the
induction of tumor-specific T cells targeting human
leukocyte antigens (HLA)-presented peptides. Our work aimed
to analyze the landscape of naturally presented HLA class I
and II ligands of primary ependymomas (EPN) to delineate
EPN-associated antigens.We investigated 22 EPN tissue
samples using a comparative mass spectrometry-based
immunopeptidomic approach. Additionally, EPN-specific
antigens were functionally characterized in T-cell-based
immunogenicity assays.We discovered a subset of
EPN-exclusive peptides including HLA-A*02 and
HLA-A*25/HLA-A*26-restricted HLA ligands and identified a
small panel of cancer/testis antigens (CTAs)-derived HLA
ligands. Furthermore, we outlined immunopeptidomic
alterations in different ependymoma subgroups and
progressive ependymoma. Subsequently, we performed
functional characterization of the previously identified
HLA-A*02:01 restricted peptide FLDS to demonstrate
immunogenicity in vitro.The immunopeptidome landscape of
EPNs provides actionable targets that could further be
explored as a T cell-based immunotherapeutic strategy in
this tumor entity.},
keywords = {HLA ligands (Other) / cancer vaccination (Other) /
immunotherapy (Other) / mass spectrometry (Other) / peptide
vaccine (Other)},
cin = {TU01},
ddc = {610},
cid = {I:(DE-He78)TU01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40376681},
pmc = {pmc:PMC12080555},
doi = {10.1093/noajnl/vdae226},
url = {https://inrepo02.dkfz.de/record/301479},
}