title: Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer.
abstract: The programmed death-1 (PD-1) pathway is important in the maintenance of peripheral tolerance and homeostasis through suppression of T cell receptor signaling. As such, it is employed by many tumors as a means of immune escape. We have investigated the role of this pathway in human ovarian cancer (OC) to assess its potential role as a diagnostic and/or prognostic marker and therapeutic target, following recent clinical trial success of antibody therapy directed at this pathway. We show programmed death ligand-1 (PD-L1) expression on monocytes in the ascites and blood of patients with malignant OC is strikingly higher than those with benign/borderline disease, with no overlap in the values between these groups. We characterize the regulation of this molecule and show a role of IL-10 present in ascitic fluid. Flow cytometric analysis of T cells present in the ascites and blood showed a correlation of PD-1 expression with malignant tumors versus benign/borderline, in a similar manner to PD-L1 expression on monocytes. Finally, we demonstrate functional links between PD-L1 expression on monocytes and OC tumor cells with suppression of T cell responses. Overall, we present data based on samples obtained from women with ovarian cancer, suggesting the PD-1 pathway may be used as a reliable diagnostic marker in OC, as well as a viable target for use with PD-1/PD-L1-directed antibody immunotherapy.
authors.affiliation: Department of Medicine, Imperial College London, London, UK.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Maine
authors.forename: Nor Haslinda Abdul
authors.initials: NH
authors.lastname: Aziz
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.forename: Claudia
authors.initials: C
authors.lastname: Hayford
authors.forename: Nancy
authors.initials: N
authors.lastname: Brewig
authors.forename: Lynsey
authors.initials: L
authors.lastname: Whilding
authors.forename: Andrew J T
authors.initials: AJ
authors.lastname: George
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ghaem-Maghami
mesh_terms: D019138:Antibodies, Blocking / Q000276:immunology; D060890:B7-H1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000276:immunology; D008213:Lymphocyte Activation; D058990:Molecular Targeted Therapy / Q000379:methods*; D009000:Monocytes / Q000276:immunology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000473:pathology*; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D019139:Tumor Escape
chemical_list: D019138:Antibodies, Blocking; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10