The immunopeptidomic landscape of ovarian carcinomas

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology*
  • CA-125 Antigen / immunology
  • Carcinoma, Ovarian Epithelial
  • Female
  • GPI-Linked Proteins / immunology
  • Galectin 1 / immunology
  • Gene Expression Regulation, Neoplastic
  • HLA-DR Antigens / immunology
  • HLA-DR Antigens / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunotherapy
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Kallikreins / immunology
  • Ligands
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism*
  • Membrane Proteins / immunology
  • Neoplasms, Glandular and Epithelial / immunology
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Vaccination

Substances

  • CA-125 Antigen
  • GPI-Linked Proteins
  • Galectin 1
  • HLA-DR Antigens
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • LGALS1 protein, human
  • Ligands
  • MUC16 protein, human
  • Membrane Glycoproteins
  • Membrane Proteins
  • indoleamine 2,3-dioxygenase 1, human
  • KLK10 protein, human
  • Kallikreins
  • mesothelin