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

File Description SizeFormat 
PD-L1 ovarian CCR resubmission merged PDF.pdfAccepted version832.48 kBAdobe PDFDownload
Title: Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer
Author(s): 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.
Publication Date: 16-Dec-2016
Date of Acceptance: 8-Dec-2016
URI: http://hdl.handle.net/10044/1/43514
DOI: https://dx.doi.org/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
Sponsor/Funder: Genesis Research Trust
Cancer Research UK
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: n/a
C17375/A16989
RDB01 79560
RDB01 79560
Copyright Statement: © 2016, American Association for Cancer Research.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
INFILTRATING T-CELLS
ANTI-PD-L1 ANTIBODY
PD-L1 EXPRESSION
SURVIVAL
TUMORS
METAANALYSIS
LYMPHOCYTES
IMMUNITY
Oncology & Carcinogenesis
1112 Oncology And Carcinogenesis
Publication Status: Published
Conference Place: United States
Appears in Collections:Division of Surgery
Department of Medicine
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons