American Association for Cancer Research
10780432ccr130568-sup-fig_s1.pdf (744.37 kB)

Supplementary Figure S1 from The IL-18 Antagonist IL-18–Binding Protein Is Produced in the Human Ovarian Cancer Microenvironment

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journal contribution
posted on 2023-03-31, 17:00 authored by Grazia Carbotti, Gaia Barisione, Anna Maria Orengo, Antonella Brizzolara, Irma Airoldi, Marina Bagnoli, Patrizia Pinciroli, Delia Mezzanzanica, Maria Grazia Centurioni, Marina Fabbi, Silvano Ferrini

Supplementary Figure S1 - PDF file 744K, Receiver Operating Characteristic (ROC) curve for IL-18BP serum levels at diagnosis in patients with all types and stages of ovarian tumors (malignant n. 48 versus normal controls n. 13): the area under the curve (AUC) value is significant with the 95% confidence interval indicated in parentheses. SE=standard error



Purpose: Interleukin (IL)-18 is an immune-enhancing cytokine, which induces IFN-γ production, T-helper 1 responses, and antitumor effects. In turn, IFN-γ stimulates IL-18–binding protein production, which blocks IL-18 activity. In view of the potential use of IL-18 in epithelial ovarian cancer (EOC) immunotherapy, here, we studied IL-18BP expression and its regulation by cytokines in EOC cells in vitro and in vivo.Experimental Design: Expression and production of IL-18BP in EOC cell lines, primary ovarian carcinomas, and the corresponding normal tissues, patients' serum, and ascites were investigated by immunochemistry, ELISA, screening of gene expression profiles, and reverse-transcription PCR.Results: Analysis of gene expression profiles revealed that IL18BP mRNA is increased in EOC tumors compared with normal ovary cells. Release of IL-18BP was detectable in EOC sera and to a greater extent in the ascites, indicating production at the tumor site. Indeed, immunochemical analyses on cells isolated from the ascites and on tumor sections indicated that IL-18BP is expressed in both tumor cells and tumor-associated leukocytes, which displayed a CD3−CD20−NKp46−CD13+CD14low phenotype. EOC cell lines do not constitutively express IL-18BP. However, its release is inducible both by IFN-γ stimulation in vitro and by xenotransplantation of EOC cells in immune-deficient mice, suggesting a role for the microenvironment. In vitro experiments and immunochemistry indicated that IL-27 is also involved in IL-18BP upregulation in EOC cell lines and primary cells through STAT1 activation. Together, these data indicate that IL-18BP, which is produced in EOC in response to microenvironmental factors, may inhibit endogenous or exogenous IL-18 activity. Clin Cancer Res; 19(17); 4611–20. ©2013 AACR.

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