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@ARTICLE{Nelde:284802,
author = {A. Nelde and H. Schuster and J. Heitmann$^*$ and J. Bauer
and Y. Maringer and M. Zwick and J.-P. Volkmer and J. Y.
Chen and A. M. P. Stanger and A. Lehmann and B. Appiah and
M. Märklin$^*$ and E. Rücker-Braun and H. Salih$^*$ and M.
Roerden and S. M. Schroeder and M.-F. Häring and A.
Schlosser and J. Schetelig and M. Schmitz$^*$ and M.
Börries$^*$ and N. Köhler and C. Lengerke$^*$ and R.
Majeti and I. L. Weissman and H.-G. Rammensee$^*$ and J.
Walz$^*$},
title = {{I}mmune {S}urveillance of {A}cute {M}yeloid {L}eukemia
{I}s {M}ediated by {HLA}-{P}resented {A}ntigens on
{L}eukemia {P}rogenitor {C}ells.},
journal = {Blood cancer discovery},
volume = {4},
number = {6},
issn = {2643-3230},
address = {Philadelphia, PA},
publisher = {American Association for Cancer Research},
reportid = {DKFZ-2023-02105},
pages = {468-489},
year = {2023},
note = {2023 Nov 1;4(6):468-489},
abstract = {Therapy-resistant leukemia stem and progenitor cells (LSC)
are a main cause of acute myeloid leukemia (AML) relapse.
LSC-targeting therapies may thus improve outcome of patients
with AML. Here we demonstrate that LSCs present
HLA-restricted antigens that induce T-cell responses
allowing for immune surveillance of AML. Using a mass
spectrometry-based immunopeptidomics approach, we
characterized the antigenic landscape of patient LSCs and
identified AML- and AML/LSC-associated HLA-presented
antigens absent from normal tissues comprising nonmutated
peptides, cryptic neoepitopes, and neoepitopes of common AML
driver mutations of NPM1 and IDH2. Functional relevance of
shared AML/LSC antigens is illustrated by presence of their
cognizant memory T cells in patients. Antigen-specific
T-cell recognition and HLA class II immunopeptidome
diversity correlated with clinical outcome. Together, these
antigens shared among AML and LSCs represent prime targets
for T cell-based therapies with potential of eliminating
residual LSCs in patients with AML.The elimination of
therapy-resistant leukemia stem and progenitor cells (LSC)
remains a major challenge in the treatment of AML. This
study identifies and functionally validates LSC-associated
HLA class I and HLA class II-presented antigens, paving the
way to the development of LSC-directed T cell-based
immunotherapeutic approaches for patients with AML. See
related commentary by Ritz, p. 437 .},
cin = {TU01 / DD01 / FR01},
ddc = {610},
cid = {I:(DE-He78)TU01-20160331 / I:(DE-He78)DD01-20160331 /
I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37847741},
doi = {10.1158/2643-3230.BCD-23-0020},
url = {https://inrepo02.dkfz.de/record/284802},
}