TY  - JOUR
AU  - Nelde, Annika
AU  - Schuster, Heiko
AU  - Heitmann, Jonas
AU  - Bauer, Jens
AU  - Maringer, Yacine
AU  - Zwick, Melissa
AU  - Volkmer, Jens-Peter
AU  - Chen, James Y
AU  - Stanger, Anna M Paczulla
AU  - Lehmann, Ariane
AU  - Appiah, Bismark
AU  - Märklin, Melanie
AU  - Rücker-Braun, Elke
AU  - Salih, Helmut
AU  - Roerden, Malte
AU  - Schroeder, Sarah M
AU  - Häring, Max-Felix
AU  - Schlosser, Andreas
AU  - Schetelig, Johannes
AU  - Schmitz, Marc
AU  - Börries, Melanie
AU  - Köhler, Natalie
AU  - Lengerke, Claudia
AU  - Majeti, Ravindra
AU  - Weissman, Irving L
AU  - Rammensee, Hans-Georg
AU  - Walz, Juliane
TI  - Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.
JO  - Blood cancer discovery
VL  - 4
IS  - 6
SN  - 2643-3230
CY  - Philadelphia, PA
PB  - American Association for Cancer Research
M1  - DKFZ-2023-02105
SP  - 468-489
PY  - 2023
N1  - 2023 Nov 1;4(6):468-489
AB  - 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 .
LB  - PUB:(DE-HGF)16
C6  - pmid:37847741
DO  - DOI:10.1158/2643-3230.BCD-23-0020
UR  - https://inrepo02.dkfz.de/record/284802
ER  -