Modulation of interleukin-18 expression in human colon carcinoma: consequences for tumor immune surveillance

Int J Cancer. 1999 Jun 21;84(3):326-30. doi: 10.1002/(sici)1097-0215(19990621)84:3<326::aid-ijc22>;2-k.


The production in colon cancer of interferon-gamma (IFN-gamma), 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-gamma 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-gamma 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-gamma 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-gamma production and Fas-L-dependent cytotoxicity of immune cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / genetics
  • Colon / metabolism
  • Colonic Neoplasms / immunology*
  • Fas Ligand Protein
  • Humans
  • Interferon-gamma / analysis
  • Interleukin-18 / biosynthesis*
  • Interleukin-18 / genetics
  • Intestinal Mucosa / metabolism
  • Membrane Glycoproteins / analysis
  • RNA, Messenger / analysis
  • Tumor Cells, Cultured


  • FASLG protein, human
  • Fas Ligand Protein
  • Interleukin-18
  • Membrane Glycoproteins
  • RNA, Messenger
  • Interferon-gamma
  • Caspase 1