Role of the endogenous production of interleukin 12 in immunotherapy.

Abstract

Previous studies demonstrated that injecting mice with the cytokine interleukin 12 (IL-12) could significantly suppress the growth of a number of tumors, including murine B16 melanoma. In this report, the persistence of the antitumor effects of IL-12 is investigated. The i.p. injection of IL-12 (0.1 microg) on days 14, 16, 18, 20, and 22 was found to significantly suppress the growth of s.c. inoculated B16 melanoma for up to 2 weeks after the last injection of IL-12. Interestingly, the IL-12 serum level 4 days after the last injection of IL-12 was significantly elevated in tumor-bearing mice compared with that of IL-12-treated normal mice. The in vivo depletion of either CD4+ or CD8+ T cells abrogated the antitumor activity of IL-12 and diminished the apparent autocrine stimulation of IL-12 release seen after IL-12 treatment. Resection of the tumor-draining lymph nodes (LNs) but not of the spleen abrogated the antitumor effect of IL-12 treatment as well as the elevation of serum IL-12. Expression of mRNA encoding IL-12 as well as CD40 ligand (CD40L) was detected in the tumor-draining LNs but not in the spleen of tumor-bearing mice after IL-12 treatment. Furthermore, the antitumor activity observed after IL-12 treatment was diminished by the in vivo administration of either anti-IL-12 or anti-CD40L monoclonal antibodies. Collectively, these results suggest that the endogenous production of IL-12 resulting from the CD40-CD40L interaction between antigen-presenting cells and CD4+ T cells in the tumor-draining LNs may play a role in the persistence of the antitumor effects seen after IL-12 treatment.

• Authors: M Harada, K Tamada, K Abe, K Yasumoto, G Kimura, K Nomoto
• Journal: Cancer research (Cancer Res) Vol. 58 Issue 14 Pg. 3073-7 (Jul 15 1998) ISSN: 0008-5472 [Print] United States
• PMID: 9679973 (Publication Type: Journal Article)

Chemical References

• CD40 Antigens
• Interleukin-12

Topics

• Animals
• CD4-Positive T-Lymphocytes (immunology)
• CD40 Antigens (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Female
• Immunotherapy
• Interleukin-12 (administration & dosage, biosynthesis, blood, immunology)
• Melanoma, Experimental (blood, immunology, therapy)
• Mice
• Mice, Inbred C57BL
• Tumor Cells, Cultured