The immunopeptidomic landscape of ovarian carcinomas
| Autor: | Oliver Kohlbacher, Kevin Röhle, Barbara Schmid-Horch, Stefan Stevanovic, Nico Trautwein, Daniel J. Kowalewski, Tatjana Bilich, Britta Ney, Armin Rabsteyn, Heiko Schuster, Janet Kerstin Peper, Annette Staebler, Sara Y. Brucker, T Engler, Sabine Braun, Sebastian P. Haen, Hans-Christian Bösmüller, Linus Backert, Falko Fend, Markus W. Löffler, Juliane S. Walz, Hans-Georg Rammensee, Diethelm Wallwiener, Philipp Wagner |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
endocrine system diseases immunopeptidome Galectin 1 medicine.medical_treatment Antigen presentation Human leukocyte antigen Carcinoma Ovarian Epithelial GPI-Linked Proteins Ligands 03 medical and health sciences 0302 clinical medicine Immunology and Inflammation Antigen Cancer immunotherapy medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Mesothelin mucin 16 Neoplasms Glandular and Epithelial Ovarian Neoplasms Antigen Presentation Multidisciplinary Membrane Glycoproteins biology Histocompatibility Antigens Class I Vaccination Histocompatibility Antigens Class II Membrane Proteins Immunotherapy HLA-DR Antigens Biological Sciences mesothelin medicine.disease female genital diseases and pregnancy complications Gene Expression Regulation Neoplastic 030104 developmental biology ovarian cancer PNAS Plus 030220 oncology & carcinogenesis CA-125 Antigen Cancer cell Immunology biology.protein Female Kallikreins Ovarian cancer |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Significance Despite the revolution in cancer therapy initiated by checkpoint inhibitors, durable clinical responses remain sporadic in many types of cancer, including ovarian cancer. Understanding which antigens are essentially presented by tumor cells and further able to be recognized by T cells provides a major step toward novel effective targeted immunotherapies. In this study, we comprehensively analyzed the immunopeptidomic landscape of ovarian carcinoma and compared it to variety of benign sources to identify antigens exclusively presented on tumor cells. With personalized therapies moving into the focus of clinical cancer therapy, we further present insights on how gene-expression analysis and immunohistochemistry can support antigen selection for individualized immunotherapy. 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. |
| Databáze: | OpenAIRE |
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