American Association for Cancer Research
bcd-23-0020_supplementary_figures_s1-s13_suppsf1.pdf (7 MB)

Supplementary Figures S1-S13 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 Figures file includes Figures S1 to S13. Figure S1: Gating strategy for the evaluation of LSC frequencies pre and post enrichment. Figure S2: Amino acid distribution within LSC and AML bulk immunopeptidomes. Figure S3: HLA class I immunopeptidomics. Figure S4: Abundance of AML- and AML/LSC-associated HLA class I ligands within the immunopeptidome. Figure S5: Identification of AML- and AML/LSC-associated HLA class II antigen targets by comparative immunopeptidome profiling. Figure S6: Abundance of AML- and AML/LSC-associated HLA class II peptides within the immunopeptidome. Figure S7: Spectral validation of HLA class I-restricted AML- and AML/LSC-associated peptides. Figure S8: Spectral validation of HLA class II-restricted AML- and AML/LSC-associated peptides. Figure S9: Magnitude and functionality of in vitro primed CD8+ T cells. Figure S10: Characterization of memory T cell responses detected in ELISpot assays. Figure S11: Further characterization of HLA class II-restricted antigens. Figure S12: In-depth characterization and phenotyping of HLA class II AML/LSC-specific CD4+ T cells by single-cell RNA sequencing and multi-color flow cytometry. Figure S13: Impact of immunopeptidome diversity and peptide-specific immune responses on patient survival.


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



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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