Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer

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. Immune cells were separated from blood, asc...

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Bibliographic Details
Published in:Clinical cancer research 2017-07, Vol.23 (13), p.3453-3460
Main Authors: Chatterjee, Jayanta, Dai, Wei, Aziz, Nor Haslinda Abd, Teo, Pei Yun, Wahba, John, Phelps, David L, Maine, Christian J, Whilding, Lynsey M, Dina, Roberto, Trevisan, Giorgia, Flower, Kirsty J, George, Andrew J T, Ghaem-Maghami, Sadaf
Format: Article
Language:English
Subjects:
Adult
Aged
Apoptosis
Ascites
B7-H1 Antigen - blood
Benign
Biomarkers
Biomarkers, Tumor - blood
Blood
CA-125 Antigen - blood
CA-125 Antigen - immunology
Cancer
CD11c antigen
CD14 antigen
Cell death
Cytometry
Diagnostic systems
Disease-Free Survival
Enzyme-linked immunosorbent assay
Experimental design
Female
Flow cytometry
Gene Expression Regulation, Neoplastic - immunology
Histology
Humans
Immune system
Immunohistochemistry
Immunology
Inflammation
Kaplan-Meier Estimate
Ligands
Lymphocytes
Medical prognosis
Middle Aged
Monocytes
Mortality
Ovarian cancer
Ovarian Neoplasms - blood
Ovarian Neoplasms - genetics
Ovarian Neoplasms - immunology
Ovarian Neoplasms - pathology
Patients
PD-1 protein
PD-L1 protein
Prognosis
Programmed Cell Death 1 Receptor - blood
Tumor markers
Tumors
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Summary: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. 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. 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. 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. .
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.ccr-16-2366