A meta-analysis of HLA peptidome composition in different hematological entities: entity-specific dividing lines and "pan-leukemia" antigens
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Linus Backert1,2,*, Daniel Johannes Kowalewski1,3,*, Simon Walz1,4, Heiko Schuster1,3, Claudia Berlin1,4, Marian Christoph Neidert5, Mirle Schemionek6, Tim H. Brümmendorf6, Vladan Vucinic7, Dietger Niederwieser7, Lothar Kanz4, Helmut Rainer Salih4,8, Oliver Kohlbacher2,9,10, Katja Weisel4, Hans-Georg Rammensee1,11, Stefan Stevanović1,11 and Juliane Sarah Walz4
1Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany
2Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany
3Immatics Biotechnologies GmbH, Tübingen, Germany
4Department of Hematology and Oncology, University of Tübingen, Tübingen, Germany
5Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland
6Department of Hematology, Oncology, Hemostaseology and SCT, University Hospital RWTH Aachen, Aachen, Germany
7University Hospital Leipzig, Department of Hematology and Oncology, Leipzig, Germany
8Clinical Cooperation Unit Translational Immunology, German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany
9Quantitative Biology Center, University of Tübingen, Tübingen, Germany
10Biomolecular Interactions, Max Planck Institute for Developmental Biology, Tübingen, Germany
11German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany
*These authors have contributed equally to this work
Juliane Sarah Walz, email: [email protected]
Keywords: hematological malignancies, cancer immunotherapy, tumor antigen, HLA, mass spectrometry
Received: August 24, 2016 Accepted: December 26, 2016 Published: January 31, 2017
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape. We found the cancer HLA peptidome datasets to cluster specifically along entity and lineage lines, suggesting that the immunopeptidome directly reflects the differences in the underlying (tumor-)biology. In line with these findings, we only detected a small set of entity-spanning antigens, which were predominantly characterized by low presentation frequencies within the different patient cohorts. These findings suggest that design of T-cell immunotherapies for the treatment of HM should ideally be conducted in an entity-specific fashion.
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