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Supplementary Tables S1 to S15 from Immune Surveillance of Acute Myeloid Leukemia Is Mediated by HLA-Presented Antigens on Leukemia Progenitor Cells

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posted on 2024-01-25, 15:01 authored by Annika Nelde, Heiko Schuster, Jonas S. Heitmann, Jens Bauer, Yacine Maringer, Melissa Zwick, Jens-Peter Volkmer, James Y. Chen, Anna M. Paczulla Stanger, Ariane Lehmann, Bismark Appiah, Melanie Märklin, Elke Rücker-Braun, Helmut R. Salih, Malte Roerden, Sarah M. Schroeder, Max-Felix Häring, Andreas Schlosser, Johannes Schetelig, Marc Schmitz, Melanie Boerries, Natalie Köhler, Claudia Lengerke, Ravindra Majeti, Irving L. Weissman, Hans-Georg Rammensee, Juliane S. Walz

The Supplementary Tables file includes Tables S1 to S15. Table S1: Frequencies of CD34+CD38- LSCs within primary AML patient samples. Table S2: Immunopeptidomics cohort overview. Table S3: Patient characteristics of AML immunopeptidomics cohort. Table S4: AML- and AML/LSC-associated HLA class I targets. Table S5: AML/LSC shared HLA class I-presented antigens. Table S6: AML- and AML/LSC-associated HLA class II peptide, protein, and hotspot targets. Table S7: AML/LSC shared HLA class II-presented peptide targets. Table S8: Recurrent AML mutations included in neoepitope screening. Table S9: Characteristics of AML patient samples used for T cell-based assays. Table S10: Characteristics of HV samples used for T cell-based assays. Table S11: Immunopeptidome diversity according to demographics and disease characteristics. Table S12: Impact of demographics and disease characteristics on patient outcome in the immunopeptidome survival analysis group. Table S13: Patient characteristics of immunopeptidome survival analysis group. Table S14: Patient characteristics of immune response survival analysis group. Table S15: Impact of demographics and hematopoietic stem cell transplantation on patient outcome in the immune response survival group.

Funding

Deutsche Forschungsgemeinschaft (DFG)

Federal Ministry of Education and Research

German Cancer Consortium

Ernst Jung Prize for Medicine

Landesforschungspreis of Baden-Württemberg

Wilhelm Sander-Stiftung (Wilhelm Sander Foundation)

Jose Carreras Leukämie Stiftung

Deutsche Krebshilfe (German Cancer Aid)

Swiss National Science Foundation

European Research Council

Else Kröner-Fresenius-Stiftung (EKFS)

Fortüne Programm of the University of Tübingen

Fortüne Program of the University of Tübingen

History

ARTICLE 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. 430.This article is featured in Selected Articles from This Issue, p. 419

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