Format

Send to

Choose Destination
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

1
Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany.
2
Department of Hematology and Oncology, University Hospital Tübingen, Tübingen, Germany.
3
Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany.
4
Clinical Cooperation Unit Translational Immunology, German Cancer Consortium, German Cancer Research Center (DKFZ) partner site Tübingen, Germany.
5
Immatics Biotechnologies, Tübingen, Germany.
6
Immatics US, Houston, Texas.
7
Department of Neurosurgery, Clinical Neuroscience Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland.
8
Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, University Hospital Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen, Aachen, Germany.
9
Department of Hematology and Oncology, University Hospital Leipzig, Leipzig, Germany.
10
Quantitative Biology Center, University of Tübingen, Tübingen, Germany.
11
Biomolecular Interactions, Max-Planck-Institute for Developmental Biology, Tübingen, Germany.
12
Institute for Translational Bioinformatics, University Hospital Tübingen, Tübingen, Germany; and.
13
German Cancer Consortium, DKFZ partner site Tübingen, Tübingen, Germany.

Abstract

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center