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Blood. 2015 Sep 3;126(10):1203-13. doi: 10.1182/blood-2015-04-640532. Epub 2015 Jul 2.

The antigenic landscape of multiple myeloma: mass spectrometry (re)defines targets for T-cell-based immunotherapy.

Author information

  • 1Department of Hematology and Oncology, Institute for Cell Biology, Department of Immunology, and.
  • 2Department of Hematology and Oncology.
  • 3Institute for Cell Biology, Department of Immunology, and.
  • 4Institute for Cell Biology, Department of Immunology, and Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany;
  • 5Department of Orthopedics, Hospital Group South-West, Calw, Germany; and.
  • 6Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, Tübingen, Germany;
  • 7Department of Hematology and Oncology, Clinical Cooperation Unit Translational Immunology and.
  • 8Institute for Cell Biology, Department of Immunology, and Cancer Immunotherapy Unit, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Partner Site Tübingen, Tübingen, Germany.

Erratum in

  • Blood. 2015 Oct 22;126(17):2072-3.

Abstract

Direct analysis of HLA-presented antigens by mass spectrometry provides a comprehensive view on the antigenic landscape of different tissues/malignancies and enables the identification of novel, pathophysiologically relevant T-cell epitopes. Here, we present a systematic and comparative study of the HLA class I and II presented, nonmutant antigenome of multiple myeloma (MM). Quantification of HLA surface expression revealed elevated HLA molecule counts on malignant plasma cells compared with normal B cells, excluding relevant HLA downregulation in MM. Analyzing the presentation of established myeloma-associated T-cell antigens on the HLA ligandome level, we found a substantial proportion of antigens to be only infrequently presented on primary myelomas or to display suboptimal degrees of myeloma specificity. However, unsupervised analysis of our extensive HLA ligand data set delineated a panel of 58 highly specific myeloma-associated antigens (including multiple myeloma SET domain containing protein) which are characterized by frequent and exclusive presentation on myeloma samples. Functional characterization of these target antigens revealed peptide-specific, preexisting CD8(+) T-cell responses exclusively in myeloma patients, which is indicative of pathophysiological relevance. Furthermore, in vitro priming experiments revealed that peptide-specific T-cell responses can be induced in response-naive myeloma patients. Together, our results serve to guide antigen selection for T-cell-based immunotherapy of MM.

PMID:
26138685
PMCID:
PMC4608392
DOI:
10.1182/blood-2015-04-640532
[PubMed - indexed for MEDLINE]
Free PMC Article
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