Immune surveillance of acute myeloid leukemia is mediated by HLA-presented antigens on leukemia progenitor cells

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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.
Significance:

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Blood cancer discovery. - 4, 6 (2023) , 468-489, ISSN: 2643-3249

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2023
Urheber

DOI
10.1158/2643-3230.bcd-23-0020
URN
urn:nbn:de:bsz:25-freidok-2416866
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:39 MESZ

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  • 2023

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