The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy
| Autor: | Malte Roerden, Reinhild Klein, Jonas Rieth, Stefan Stevanovic, Ana Marcu, Tim H. Brümmendorf, Annika Nelde, Vladan Vucinic, Juliane S. Walz, Mirle Schemionek, Daniel J. Kowalewski, Jens Bauer, Dietger Niederwieser, Maren Lübke, Heiko Schuster, Leon Bichmann, Janet Kerstin Peper, Marian Christoph Neidert, Hans-Georg Rammensee, Oliver Kohlbacher, Tatjana Bilich, Melanie Märklin, Helmut R. Salih, Chih-Chiang Tsou, Lothar Kanz |
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| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine medicine.drug_class Chronic lymphocytic leukemia medicine.medical_treatment Immunology Fusion Proteins bcr-abl Epitopes T-Lymphocyte Human leukocyte antigen Ligands Biochemistry Tyrosine-kinase inhibitor 03 medical and health sciences 0302 clinical medicine Immune system Antigen Antigens Neoplasm HLA Antigens Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Humans Medicine Cytotoxic T cell neoplasms business.industry Myeloid leukemia Cell Biology Hematology Immunotherapy medicine.disease 030104 developmental biology business T-Lymphocytes Cytotoxic 030215 immunology |
| Zdroj: | Blood. 133:550-565 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Antileukemia immunity plays an important role in disease control and maintenance of tyrosine kinase inhibitor (TKI)-free remission in chronic myeloid leukemia (CML). Thus, antigen-specific immunotherapy holds promise for strengthening immune control in CML but requires the identification of CML-associated targets. In this study, we used a mass spectrometry–based approach to identify naturally presented HLA class I– and class II–restricted peptides in primary CML samples. Comparative HLA ligandome profiling using a comprehensive dataset of different hematological benign specimens and samples from CML patients in deep molecular remission delineated a panel of novel frequently presented CML-exclusive peptides. These nonmutated target antigens are of particular relevance because our extensive data-mining approach suggests the absence of naturally presented BCR-ABL– and ABL-BCR–derived HLA-restricted peptides and the lack of frequent tumor-exclusive presentation of known cancer/testis and leukemia-associated antigens. Functional characterization revealed spontaneous T-cell responses against the newly identified CML-associated peptides in CML patient samples and their ability to induce multifunctional and cytotoxic antigen-specific T cells de novo in samples from healthy volunteers and CML patients. Thus, these antigens are prime candidates for T-cell–based immunotherapeutic approaches that may prolong TKI-free survival and even mediate cure of CML patients. |
| Databáze: | OpenAIRE |
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