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Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer

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Title: Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer
Authors: Chatterjee, J
Dai, W
Abd Aziz, NH
Teo, PY
Wahba, J
Phelps, DL
Maine, CJ
Whilding, L
Dina, R
Trevisan, G
Flower, K
George, A
Ghaem-Maghami, S
Item Type: Journal Article
Abstract: Purpose We aimed to establish whether PD-1 and PD-L1 expression, in ovarian cancer (OC) tumour tissue and blood, could be used as biomarkers for discrimination of tumour histology and prognosis of OC. Experimental Design Immune cells were separated from blood, ascites and tumour tissue obtained from women with suspected OC and studied for the differential expression of possible immune biomarkers using flow cytometry. PD-L1 expression on tumour 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 tumours and epithelial ovarian cancers (EOC) - 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 tumour marker CA-125 alone. Plasma soluble PD-L1 was elevated in EOC patients compared to healthy women and patients with benign ovarian tumours. 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.
Issue Date: 16-Dec-2016
Date of Acceptance: 8-Dec-2016
URI: http://hdl.handle.net/10044/1/43514
DOI: 10.1158/1078-0432.CCR-16-2366
ISSN: 1557-3265
Publisher: American Association for Cancer Research
Start Page: 3453
End Page: 3460
Journal / Book Title: Clinical Cancer Research
Volume: 23
Issue: 13
Copyright Statement: © 2016, American Association for Cancer Research.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Genesis Research Trust
Cancer Research UK
Funder's Grant Number: RDB01 79560
RDB01 79560
n/a
16989
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
INFILTRATING T-CELLS
ANTI-PD-L1 ANTIBODY
PD-L1 EXPRESSION
SURVIVAL
TUMORS
METAANALYSIS
LYMPHOCYTES
IMMUNITY
Adult
Aged
B7-H1 Antigen
Biomarkers, Tumor
CA-125 Antigen
Disease-Free Survival
Female
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
Middle Aged
Ovarian Neoplasms
Prognosis
Programmed Cell Death 1 Receptor
Humans
Ovarian Neoplasms
CA-125 Antigen
Prognosis
Disease-Free Survival
Gene Expression Regulation, Neoplastic
Adult
Aged
Middle Aged
Female
Kaplan-Meier Estimate
Programmed Cell Death 1 Receptor
Biomarkers, Tumor
B7-H1 Antigen
1112 Oncology and Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Conference Place: United States
Online Publication Date: 2016-12-16
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine