Ovarian cancer-associated ascites demonstrates altered immune environment: Implications for antitumor immunity

Robert L. Giuntoli, Tonya J. Webb, Alessia Zoso, Ophelia Rogers, Teresa P. Diaz-Montes, Robert E. Bristow, Mathias Oelke

Research output: Contribution to journalArticlepeer-review

Abstract

Background: To identify immunosuppressive elements present in ovarian cancer associated ascites. Patients and Methods: Ascites and plasma were obtained from ovarian, primary peritoneal or fallopian tube cancer patients. Surface markers were identified by fluorescence-activated cell sorting (FACS). Cytokine and chemokine concentrations were measured with LINCOplex microarrays. Antigen-specific T-lymphocytes from ascites and plasma were expanded with artificial antigen-presenting cells (aAPC). Cell-mediated immune response was assessed with chromium release assays. Results: Samples were collected from 37 patients with advanced ovarian cancer. FACS was performed on 27 ascites specimens. A low CD4/CD8 ratio (<1.6) was seen in 13 patient samples and associated with significantly improved overall survival (p=0.040). LINCOplex evaluation of 22 paired ascites and plasma samples demonstrated significantly elevated levels of IL-6, IL-8, IL-10, IL-15, IP-10, MCP-1, MIP-1β and VEGF and significantly reduced levels of IL-2, IL-5, IL-7, IL-17, PDGF-BB, and RANTES in ascites compared to plasma (p<0.05). Autologous ovarian cancer cell lysis with T-lymphocytes from ascites was limited. Although aAPC stimulation resulted in effective expansion of antigen specific T-cells from peripheral lymphocytes (35-fold), only limited expansion was noted from ascites-derived lymphocytes (10-fold). Conclusion: Ovarian cancer-associated ascites may provide an immunosuppressive environment. A high CD4/CD8 ratio, which may indicate the presence of regulatory T-cells, is associated with poor outcome. Reduced IL-2 and elevated IL-6 and IL-10 levels favor a Th2 inhibitory immune response. This immunosuppressive climate may explain our observation of non responsiveness in ascites derived T-cells.

Original languageEnglish (US)
Pages (from-to)2875-2884
Number of pages10
JournalAnticancer Research
Volume29
Issue number8
StatePublished - Aug 1 2009

Keywords

  • Ascites
  • Cell mediated immunity
  • Chemokines
  • Cytokines
  • Ovarian cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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