3 years ago

The immunopeptidomic landscape of ovarian carcinomas [Immunology and Inflammation]

The immunopeptidomic landscape of ovarian carcinomas [Immunology and Inflammation]
Daniel J. Kowalewski, Hans–Christian Bosmuller, Diethelm Wallwiener, Sebastian P. Haen, Hans–Georg Rammensee, Tobias Engler, Falko Fend, Stefan Stevanović, Sabine Braun, Tatȷana Bilich, Armin Rabsteyn, Markus W. Loffler, Janet K. Peper, Juliane S. Walz, Linus Backert, Philipp Wagner, Heiko Schuster, Kevin Rohle, Oliver Kohlbacher, Britta Ney, Annette Staebler, Barbara Schmid–Horch, Nico Trautwein, Sara Y. Brucker

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.

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