Cytokine profiles in cyst fluids from ovarian tumors reflect immunosuppressive state of the tumor

Abstract

OBJECTIVE: Ovarian tumors, both benign and malignant, often contain cystic lesions. Analysis of cytokine levels of this enclosed fluid may be a pure way to study cytokine expression to gain more insight in tumor-host interaction. METHODS: We analyzed the expression of cytokines in 45 cyst fluids from benign and malignant ovarian tumors and mapped the cytokine profiles for the different histological subgroups. The concentration of interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, interferon gamma, tumor necrosis factor alpha, tumor necrosis factor beta, transforming growth factor beta, and C-C motif chemokine 22 was measured. RESULTS: The presence of IL-6 in cyst fluid is correlated with malignancy. IL-8 was also expressed in benign samples, but the levels were significantly higher in malignant cyst fluids. Transforming growth factor beta was only present in latent form in both benign and malignant cyst fluids. C-C motif chemokine 22 was detectable in higher levels in mucinous samples than in serous samples. IL-10 was not expressed in cyst fluid. T helper 1 subtype (TH1: IL-12 and IFN-gamma) and TH2 (IL-4, IL-5) cytokines were similarly expressed in malignant and benign mucinous tumors. However, in the serous group, TH1 and TH2 cytokines were expressed in the benign samples but not in the malignant samples. In the high-grade malignant serous group, we found an inverse relationship between IL-8 levels and overall survival. CONCLUSIONS: Our results suggest that the immunosuppressive state created by ovarian cancer is reflected in the cystic fluid within the tumor. Furthermore, our findings suggest that type 1 and type 2 tumors have a distinct immunological profile and support the dualistic model for ovarian tumorigenesis.