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Blood. 2019 Feb 7;133(6):550-565. doi: 10.1182/blood-2018-07-866830. Epub 2018 Dec 10.

The HLA ligandome landscape of chronic myeloid leukemia delineates novel T-cell epitopes for immunotherapy.

Author information

Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
Department of Hematology and Oncology, University Hospital Tübingen, Tübingen, Germany.
Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany.
Clinical Cooperation Unit Translational Immunology, German Cancer Consortium, German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
Immatics Biotechnologies, Tübingen, Germany.
Immatics US, Houston, Texas.
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
Department of Hematology and Oncology, University Hospital Leipzig, Leipzig, Germany.
Quantitative Biology Center, University of Tübingen, Tübingen, Germany.
Biomolecular Interactions, Max-Planck-Institute for Developmental Biology, Tübingen, Germany.
Institute for Translational Bioinformatics, University Hospital Tübingen, Tübingen, Germany; and.
German Cancer Consortium, DKFZ partner site Tübingen, Tübingen, Germany.


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.

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