Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells.

Autor:	Nelde A; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Schuster H; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany., Heitmann JS; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Bauer J; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Maringer Y; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany., Zwick M; Department of Medicine I, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Volkmer JP; Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, California., Chen JY; Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, California., Stanger AMP; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.; Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland., Lehmann A; Faculty of Medicine, Medical Center, Institute of Medical Bioinformatics and Systems Medicine (IBSM), University of Freiburg, Germany., Appiah B; Faculty of Medicine, Medical Center, Institute of Medical Bioinformatics and Systems Medicine (IBSM), University of Freiburg, Germany., Märklin M; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Rücker-Braun E; Department of Medicine I, University Hospital of Dresden, Dresden, Germany.; Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany., Salih HR; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany., Roerden M; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany., Schroeder SM; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Otorhinolaryngology, Head and Neck Surgery, University of Tübingen, Tübingen, Germany., Häring MF; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany., Schlosser A; Rudolf-Virchow-Zentrum, University Würzburg, Würzburg, Germany., Schetelig J; Department of Medicine I, University Hospital of Dresden, Dresden, Germany.; German Bone Marrow Donor Center (DKMS), Clinical Trials Unit, Dresden, Germany., Schmitz M; Institute of Immunology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; National Center for Tumor Diseases (NCT), University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.; German Cancer Consortium (DKTK), partner site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Boerries M; Faculty of Medicine, Medical Center, Institute of Medical Bioinformatics and Systems Medicine (IBSM), University of Freiburg, Germany.; Comprehensive Cancer Center Freiburg (CCCF), Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; German Cancer Consortium (DKTK), Partner Site, Freiburg, and German Cancer Research Center (DKFZ), Heidelberg, Germany., Köhler N; Department of Medicine I, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, Freiburg, Germany., Lengerke C; Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tübingen, Tübingen, Germany.; Department of Biomedicine, University of Basel and University Hospital Basel, Basel, Switzerland.; Clinic for Hematology, University of Basel and University Hospital Basel, Basel, Switzerland.; German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Germany., Majeti R; Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, California.; Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, California., Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine and the Ludwig Cancer Center, Stanford University School of Medicine, Stanford, California., Rammensee HG; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; German Cancer Consortium (DKTK), DKFZ partner site Tübingen, Germany., Walz JS; Department of Peptide-Based Immunotherapy, University and University Hospital Tübingen, Tübingen, Germany.; Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.; Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of Tübingen, Tübingen, Germany.; Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, Tübingen, Germany.
Jazyk:	angličtina
Zdroj:	Blood cancer discovery [Blood Cancer Discov] 2023 Nov 01; Vol. 4 (6), pp. 468-489.
DOI:	10.1158/2643-3230.BCD-23-0020
Abstrakt:	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. See related commentary by Ritz, p. 430 . This article is featured in Selected Articles from This Issue, p. 419. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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