Potent antitumor activity of interleukin-27.

Abstract

Although much promising data that interleukin (IL)-12 could be a powerful therapeutic agent against cancer were reported in animal models, its excessive toxicity has become a problem for its clinical application. IL-27 is a novel IL-12 family member that plays a role in the early regulation of T helper cell 1 initiation, including induction of T-bet and IL-12 receptor beta 2 expression. In the present study, we have evaluated the antitumor activity of IL-27 against a murine tumor model of colon carcinoma C26. C26 cells, which were transduced with the single-chain IL-27 cDNA and became secreting IL-27 (C26-IL-27), exhibited minimal tumor growth in vivo, and all of the mice inoculated with these cells survived healthily with complete tumor remission. Inoculation of mice with C26-IL-27 induced enhanced IFN-gamma production and cytotoxic T-lymphocyte activity against C26 tumor in spleen cells. Recovered mice from the inoculation showed a tumor-specific protective immunity to the following challenge with parental C26 tumor. The antitumor activity of IL-27 was almost diminished in nude mice, and depletion of CD8(+) T cells and neutralization of IFN-gamma in immunocompetent mice reduced greatly the antitumor activity. Moreover, the antitumor activity was abolished in T-bet-deficient mice, whereas it was observed unexpectedly in mice deficient of signal transducer and activator of transcription (STAT) 4. These results suggest that IL-27 has potent abilities to induce tumor-specific antitumor activity and protective immunity and that the antitumor activity is mediated mainly through CD8(+) T cells, IFN-gamma, and T-bet but not through STAT4.

• Authors: Masayuki Hisada, Sadahiro Kamiya, Koji Fujita, Maria Laura Belladonna, Tatuya Aoki, Yasuhisa Koyanagi, Junichiro Mizuguchi, Takayuki Yoshimoto
• Journal: Cancer research (Cancer Res) Vol. 64 Issue 3 Pg. 1152-6 (Feb 01 2004) ISSN: 0008-5472 [Print] United States
• PMID: 14871851 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA-Binding Proteins
• Il27 protein, mouse
• Interleukins
• STAT4 Transcription Factor
• Stat4 protein, mouse
• T-Box Domain Proteins
• T-box transcription factor TBX21
• Trans-Activators
• Transcription Factors
• Interferon-gamma

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Colonic Neoplasms (genetics, immunology, therapy)
• DNA-Binding Proteins (immunology)
• Female
• Interferon-gamma (biosynthesis, immunology)
• Interleukins (biosynthesis, genetics, immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• STAT4 Transcription Factor
• T-Box Domain Proteins
• T-Lymphocytes, Cytotoxic (immunology)
• Trans-Activators (immunology)
• Transcription Factors (biosynthesis, immunology)
• Transfection