Clinical use of programmed cell death-1 (PD-1) and its ligand (PD-L1) expression as discriminatory and predictive markers in ovarian cancer
File(s)PD-L1 ovarian CCR resubmission merged PDF.pdf (832.48 KB)
Accepted version
Author(s)
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.
Date Issued
2016-12-16
Date Acceptance
2016-12-08
Citation
Clinical Cancer Research, 2016, 23 (13), pp.3453-3460
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
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Genesis Research Trust
Cancer Research UK
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27986748
PII: 1078-0432.CCR-16-2366
Grant Number
RDB01 79560
RDB01 79560
n/a
16989
Subjects
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
Coverage Spatial
United States
Date Publish Online
2016-12-16