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Proc Natl Acad Sci U S A. 2017 Nov 14;114(46):E9942-E9951. doi: 10.1073/pnas.1707658114. Epub 2017 Nov 1.

The immunopeptidomic landscape of ovarian carcinomas.

Author information

1
Department of Immunology, Institute of Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
2
Immatics Biotechnologies GmbH, 72076 Tübingen, Germany.
3
Institute of Pathology, University Hospital of Tübingen, 72076 Tübingen, Germany.
4
Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tübingen, 72074 Tübingen, Germany.
5
Department of General, Visceral and Transplant Surgery, University Hospital of Tübingen, 72076 Tübingen, Germany.
6
German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tübingen, 72076 Tübingen, Germany.
7
Department of Obstetrics and Gynecology, University Hospital of Tübingen, 72076 Tübingen, Germany.
8
Department of Hematology and Oncology, University Hospital of Tübingen, 72076 Tübingen, Germany.
9
Department of Clinical and Experimental Transfusion Medicine, University Hospital of Tübingen, 72076 Tübingen, Germany.
10
Quantitative Biology Center, University of Tübingen, 72076 Tübingen, Germany.
11
Biomolecular interactions, Max Planck Institute for Developmental Biology, 72076 Tübingen, Germany.
12
Institute of Pathology, University Hospital of Tübingen, 72076 Tübingen, Germany; annette.staebler@med.uni-tuebingen.de.

Abstract

Immunotherapies, particularly checkpoint inhibitors, have set off a revolution in cancer therapy by releasing the power of the immune system. However, only little is known about the antigens that are essentially presented on cancer cells, capable of exposing them to immune cells. Large-scale HLA ligandome analysis has enabled us to exhaustively characterize the immunopeptidomic landscape of epithelial ovarian cancers (EOCs). Additional comparative profiling with the immunopeptidome of a variety of benign sources has unveiled a multitude of ovarian cancer antigens (MUC16, MSLN, LGALS1, IDO1, KLK10) to be presented by HLA class I and class II molecules exclusively on ovarian cancer cells. Most strikingly, ligands derived from mucin 16 and mesothelin, a molecular axis of prognostic importance in EOC, are prominent in a majority of patients. Differential gene-expression analysis has allowed us to confirm the relevance of these targets for EOC and further provided important insights into the relationship between gene transcript levels and HLA ligand presentation.

KEYWORDS:

immunopeptidome; immunotherapy; mesothelin; mucin 16; ovarian cancer

PMID:
29093164
PMCID:
PMC5699044
DOI:
10.1073/pnas.1707658114
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Conflict of interest statement: H.-G.R. is a shareholder of Immatics Biotechnologies, Tübingen, and CureVac GmbH, Tübingen. H.S. and D.J.K. are employees of Immatics Biotechnologies GmbH. The authors declare that Immatics did not provide neither financial nor scientific support in any direct relation to this manuscript or the underlying studies, and was not involved in data collection, analysis, or decision to publish.

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