title: Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer.
abstract: Purpose:We aimed to establish whether programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression, in ovarian cancer tumor tissue and blood, could be used as biomarkers for discrimination of tumor histology and prognosis of ovarian cancer.Experimental Design:Immune cells were separated from blood, ascites, and tumor tissue obtained from women with suspected ovarian cancer and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumor-associated inflammatory cells was assessed by immunohistochemistry and tissue microarray. Plasma soluble PD-L1 was measured using sandwich ELISA. The relationships among immune markers were explored using hierarchical cluster analyses.Results:Biomarkers from the discovery cohort that associated with PD-L1+cells were found. PD-L1+CD14+cells and PD-L1+CD11c+cells in the monocyte gate showed a distinct expression pattern when comparing benign tumors and epithelial ovarian cancers (EOCs)-confirmed in the validation cohort. Receiver operating characteristic curves showed PD-L1+and PD-L1+CD14+cells in the monocyte gate performed better than the well-established tumor marker CA-125 alone. Plasma soluble PD-L1 was elevated in patients with EOC compared with healthy women and patients with benign ovarian tumors. Low total PD-1+expression on lymphocytes was associated with improved survival.Conclusions:Differential expression of immunological markers relating to the PD-1/PD-L1 pathway in blood can be used as potential diagnostic and prognostic markers in EOC. These data have implications for the development and trial of anti-PD-1/PD-L1 therapy in ovarian cancer.Clin Cancer Res; 23(13); 3453-60. ©2016 AACR.
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Chatterjee
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Wei
authors.initials: W
authors.lastname: Dai
authors.affiliation: Imperial College London, London, United Kingdom.|National University of Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Nor Haslinda Abd
authors.initials: NHA
authors.lastname: Aziz
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Pei Yun
authors.initials: PY
authors.lastname: Teo
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Wahba
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: David L
authors.initials: DL
authors.lastname: Phelps
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Maine
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Lynsey M
authors.initials: LM
authors.lastname: Whilding
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Roberto
authors.initials: R
authors.lastname: Dina
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Trevisan
authors.affiliation: Imperial College London, London, United Kingdom.
authors.forename: Kirsty J
authors.initials: KJ
authors.lastname: Flower
authors.affiliation: Imperial College London, London, United Kingdom.|Brunel University London, London, United Kingdom.
authors.forename: Andrew J T
authors.initials: AJT
authors.lastname: George
authors.affiliation: Imperial College London, London, United Kingdom. s.ghaem-maghami@imperial.ac.uk.
authors.forename: Sadaf
authors.initials: S
authors.lastname: Ghaem-Maghami
mesh_terms: D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood / Q000276:immunology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor