title: Quantitative immunoproteomics analysis reveals novel MHC class I presented peptides in cisplatin-resistant ovarian cancer cells.
abstract: Platinum-based chemotherapy is widely used to treat various cancers including ovarian cancer. However, the mortality rate for patients with ovarian cancer is extremely high, largely due to chemo-resistant progression in patients who respond initially to platinum based chemotherapy. Immunotherapy strategies, including antigen specific vaccines, are being tested to treat drug resistant ovarian cancer with variable results. The identification of drug resistant specific tumor antigens would potentially provide significant improvement in effectiveness when combined with current and emerging therapies. In this study, using an immunoproteomics method based on iTRAQ technology and an LC-MS platform, we identified 952 MHC class I presented peptides. Quantitative analysis of the iTRAQ labeled MHC peptides revealed that cisplatin-resistant ovarian cancer cells display increased levels of MHC peptides derived from proteins that are implicated in many important cancer pathways. In addition, selected differentially presented epitope specific CTL recognize cisplatin-resistant ovarian cancer cells significantly better than the sensitive cells. These over-presented, drug resistance specific MHC class I associated peptide antigens could be potential targets for the development of immunotherapeutic strategies for the treatment of ovarian cancer including the drug resistant phenotype.
authors.affiliation: Immunotope, Inc., 3805 Old Easton Road, Doylestown, PA 18902, United States. vivek@immunotope.com
authors.forename: Vivekananda
authors.initials: V
authors.lastname: Shetty
authors.forename: Zacharie
authors.initials: Z
authors.lastname: Nickens
authors.forename: James
authors.initials: J
authors.lastname: Testa
authors.forename: Julie
authors.initials: J
authors.lastname: Hafner
authors.forename: Gomathinayagam
authors.initials: G
authors.lastname: Sinnathamby
authors.forename: Ramila
authors.initials: R
authors.lastname: Philip
mesh_terms: D017951:Antigen Presentation; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor; D002945:Cisplatin; D019008:Drug Resistance, Neoplasm; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D015395:Histocompatibility Antigens Class I; D009363:Neoplasm Proteins; D010455:Peptides; D002945:Cisplatin