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

Jayanta Chatterjee, Wei Dai, Abd Aziz Nor Haslinda, Pei Yun Teo, John Wahba, David L. Phelps, Christian J. Maine, Lynsey M. Whilding, Roberto Dina, Giorgia Trevisan, Kirsty J. Flower, Andrew J.T. George, Sadaf Ghaem-Maghami

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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-L1þ cells were found. PD-L1þ CD14þ cells and PD-L1þ CD11cþ 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-L1þ and PD-L1þ CD14þ 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-1þ 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.

Original languageEnglish
Pages (from-to)3453-3460
Number of pages8
JournalClinical Cancer Research
Volume23
Issue number13
DOIs
Publication statusPublished - 1 Jul 2017

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Ovarian Neoplasms
Cell Death
CD274 Antigen
Ligands
Biomarkers
Neoplasms
Tumor Biomarkers
Monocytes
Ascites
ROC Curve
Cluster Analysis
Histology
Flow Cytometry
Research Design
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Lymphocytes
Survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer. / Chatterjee, Jayanta; Dai, Wei; Nor Haslinda, Abd Aziz; 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.

In: Clinical Cancer Research, Vol. 23, No. 13, 01.07.2017, p. 3453-3460.

Research output: Contribution to journalArticle

Chatterjee, J, Dai, W, Nor Haslinda, AA, Teo, PY, Wahba, J, Phelps, DL, Maine, CJ, Whilding, LM, Dina, R, Trevisan, G, Flower, KJ, George, AJT & Ghaem-Maghami, S 2017, 'Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer', Clinical Cancer Research, vol. 23, no. 13, pp. 3453-3460. https://doi.org/10.1158/1078-0432.CCR-16-2366
Chatterjee, Jayanta ; Dai, Wei ; Nor Haslinda, Abd Aziz ; 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. / Clinical Use of Programmed Cell Death-1 and Its Ligand Expression as Discriminatory and Predictive Markers in Ovarian Cancer. In: Clinical Cancer Research. 2017 ; Vol. 23, No. 13. pp. 3453-3460.
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AU - Chatterjee, Jayanta

AU - Dai, Wei

AU - Nor Haslinda, Abd Aziz

AU - Teo, Pei Yun

AU - Wahba, John

AU - Phelps, David L.

AU - Maine, Christian J.

AU - Whilding, Lynsey M.

AU - Dina, Roberto

AU - Trevisan, Giorgia

AU - Flower, Kirsty J.

AU - George, Andrew J.T.

AU - Ghaem-Maghami, Sadaf

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N2 - 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-L1þ cells were found. PD-L1þ CD14þ cells and PD-L1þ CD11cþ 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-L1þ and PD-L1þ CD14þ 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-1þ 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.

AB - 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-L1þ cells were found. PD-L1þ CD14þ cells and PD-L1þ CD11cþ 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-L1þ and PD-L1þ CD14þ 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-1þ 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.

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