Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer

Christian J. Maine, Abd Aziz Nor Haslinda, Jayanta Chatterjee, Claudia Hayford, Nancy Brewig, Lynsey Whilding, Andrew J T George, Sadaf Ghaem-Maghami

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

The programmed death-1 (PD-1) pathway is important in the maintenance of peripheral tolerance and homeostasis through suppression of T cell receptor signaling. As such, it is employed by many tumors as a means of immune escape. We have investigated the role of this pathway in human ovarian cancer (OC) to assess its potential role as a diagnostic and/or prognostic marker and therapeutic target, following recent clinical trial success of antibody therapy directed at this pathway. We show programmed death ligand-1 (PD-L1) expression on monocytes in the ascites and blood of patients with malignant OC is strikingly higher than those with benign/borderline disease, with no overlap in the values between these groups. We characterize the regulation of this molecule and show a role of IL-10 present in ascitic fluid. Flow cytometric analysis of T cells present in the ascites and blood showed a correlation of PD-1 expression with malignant tumors versus benign/borderline, in a similar manner to PD-L1 expression on monocytes. Finally, we demonstrate functional links between PD-L1 expression on monocytes and OC tumor cells with suppression of T cell responses. Overall, we present data based on samples obtained from women with ovarian cancer, suggesting the PD-1 pathway may be used as a reliable diagnostic marker in OC, as well as a viable target for use with PD-1/PD-L1-directed antibody immunotherapy.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalCancer Immunology and Immunotherapy
Volume63
Issue number3
DOIs
Publication statusPublished - Mar 2014
Externally publishedYes

Fingerprint

Ovarian Neoplasms
Ligands
Neoplasms
Monocytes
Ascites
Peripheral Tolerance
T-Lymphocytes
Antibodies
Ascitic Fluid
T-Cell Antigen Receptor
Interleukin-10
Immunotherapy
Homeostasis
Maintenance
Clinical Trials
Therapeutics

Keywords

  • B7-H1
  • IL-10
  • Immune regulation
  • Monocytes
  • Ovarian cancer
  • PD-L1

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Immunology
  • Immunology and Allergy

Cite this

Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer. / Maine, Christian J.; Nor Haslinda, Abd Aziz; Chatterjee, Jayanta; Hayford, Claudia; Brewig, Nancy; Whilding, Lynsey; George, Andrew J T; Ghaem-Maghami, Sadaf.

In: Cancer Immunology and Immunotherapy, Vol. 63, No. 3, 03.2014, p. 215-224.

Research output: Contribution to journalArticle

Maine, Christian J. ; Nor Haslinda, Abd Aziz ; Chatterjee, Jayanta ; Hayford, Claudia ; Brewig, Nancy ; Whilding, Lynsey ; George, Andrew J T ; Ghaem-Maghami, Sadaf. / Programmed death ligand-1 over-expression correlates with malignancy and contributes to immune regulation in ovarian cancer. In: Cancer Immunology and Immunotherapy. 2014 ; Vol. 63, No. 3. pp. 215-224.
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