In a comprehensive study utilizing 42 epithelial ovarian carcinoma (EOC) bulk tumors and more than 100 benign tissue samples (5 tissue types, including ovary/fallopian tube), Schuster et al. identified over 50,000 HLA-presented peptides, including multiple HLA class I and class II peptide epitopes found exclusively on EOC tissue in >10% of patients. Priming of CD8+ T cells from healthy volunteers demonstrated the immunogenic potential of a number of these EOC-specific epitopes.
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.
Author Info: (1) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Immatics Biotechnologies GmbH, 72076 Tubingen, Germany. (2) Department of
Author Info: (1) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Immatics Biotechnologies GmbH, 72076 Tubingen, Germany. (2) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. (3) Institute of Pathology, University Hospital of Tubingen, 72076 Tubingen, Germany. (4) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. (5) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tubingen, 72074 Tubingen, Germany. (6) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. (7) Institute of Pathology, University Hospital of Tubingen, 72076 Tubingen, Germany. (8) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Department of General, Visceral and Transplant Surgery, University Hospital of Tubingen, 72076 Tubingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tubingen, 72076 Tubingen, Germany. (9) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Immatics Biotechnologies GmbH, 72076 Tubingen, Germany. (10) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. (11) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tubingen, 72076 Tubingen, Germany. (12) Department of Obstetrics and Gynecology, University Hospital of Tubingen, 72076 Tubingen, Germany. (13) Department of Obstetrics and Gynecology, University Hospital of Tubingen, 72076 Tubingen, Germany. (14) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Department of Hematology and Oncology, University Hospital of Tubingen, 72076 Tubingen, Germany. (15) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Department of Hematology and Oncology, University Hospital of Tubingen, 72076 Tubingen, Germany. (16) Department of Clinical and Experimental Transfusion Medicine, University Hospital of Tubingen, 72076 Tubingen, Germany. (17) Department of Obstetrics and Gynecology, University Hospital of Tubingen, 72076 Tubingen, Germany. (18) Department of Obstetrics and Gynecology, University Hospital of Tubingen, 72076 Tubingen, Germany. (19) Applied Bioinformatics, Center for Bioinformatics and Department of Computer Science, University of Tubingen, 72074 Tubingen, Germany. Quantitative Biology Center, University of Tubingen, 72076 Tubingen, Germany. Biomolecular interactions, Max Planck Institute for Developmental Biology, 72076 Tubingen, Germany. (20) Institute of Pathology, University Hospital of Tubingen, 72076 Tubingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tubingen, 72076 Tubingen, Germany. (21) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tubingen, 72076 Tubingen, Germany. (22) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) partner site Tubingen, 72076 Tubingen, Germany. (23) Institute of Pathology, University Hospital of Tubingen, 72076 Tubingen, Germany; annette.staebler@med.uni-tuebingen.de. (24) Department of Immunology, Institute of Cell Biology, University of Tubingen, 72076 Tubingen, Germany. Department of Obstetrics and Gynecology, University Hospital of Tubingen, 72076 Tubingen, Germany.
