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Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer
Chatterjee J, Dai W, Aziz NHA, Teo PY, Wahba J, Phelps DL, et al.
Clin Cancer Res
, 2017 07 01;23(13):3453-3460.
PMID: 27986748
DOI:
10.1158/1078-0432.CCR-16-2366
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.
Matched MeSH terms:
Antigens, CD274/blood*
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