Modulation of interleukin-18 expression in human colon carcinoma: Consequences for tumor immune surveillance
✍ Scribed by Franck Pagès; Anne Berger; Berthold Henglein; Bernard Piqueras; Claire Danel; Franck Zinzindohoue; Nicolas Thiounn; Paul H. Cugnenc; Wolf H. Fridman
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 291 KB
- Volume
- 84
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
The production in colon cancer of interferon-gamma (IFN-␥), a type-1 T-helper (TH1) cytokine, is considered as a marker of good prognosis. We asked whether interleukin-18 (IL-18), which strongly induces IFN-␥ and regulates Fas ligand (Fas-L)-dependent cytotoxicity, may play a role in colon homeostasis, and if its expression was modulated in colon adenocarcinomas. We analyzed 14 specimens of colon adenocarcinomas, 6 of normal colon mucosa of the series, and 6 colon-tumor cell lines. The expression of IL-18, of ICE protease, involved in the processing of this cytokine, and of the downstream effectors of IL-18, IFN-␥ and Fas-L was analyzed by RT-PCR. We further performed IL-18 immunostaining of normal and tumor specimens. The results were correlated with tumor dissemination and clinical outcome. We report the synthesis of IL-18 in human normal colon, mainly by epithelial cells of the mucosa. Out of the 6 tumor cell lines, 4 expressed IL-18 transcripts, but neither ICE mRNA nor secreted forms of IL-18 were detected. We observed decreased or abolished synthesis of IL-18 in colon adenocarcinomas, as compared with normal mucosa. Thus, half of the colon-cancer tissues (7/14 cases) expressed neither IFN-␥ nor Fas-L. This feature was correlated with the existence of distant metastases (Fischer's exact test, p ؍ 0.02) and an unfavorable outcome. These findings suggest that production of IL-18 in human colon may play a role in homeostasis and in tumor immune surveillance, by enhancing IFN-␥ production and Fas-L-dependent cytotoxicity of immune cells.