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

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-1beta 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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Giuntoli RL 2nd,Webb TJ,Zoso A,Rogers O,Diaz-Montes TP,Bristow RE,Oelke M

subject

Has Abstract

pub_date

2009-08-01 00:00:00

pages

2875-84

issue

8

eissn

0250-7005

issn

1791-7530

pii

29/8/2875

journal_volume

29

pub_type

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