Role of interferon-gamma in mediating the antitumor efficacy of interleukin-12

J Immunother Emphasis Tumor Immunol. 1995 Feb;17(2):71-7. doi: 10.1097/00002371-199502000-00001.


Although interleukin-12 (IL-12) has marked antitumor activity against the murine Renca renal cell carcinoma in vivo, no antiproliferative activity with IL-12 was observed against these tumor cells in vitro; in contrast, interferon-gamma (IFN-gamma) had growth inhibitory activity. Since one of the properties of IL-12 is its ability to stimulate production of IFN-gamma, the role of IFN-gamma in mediating the antitumor activity of IL-12 was evaluated. Substantially diminished antitumor activity was observed in mice injected with IL-12 and neutralizing antibody to murine IFN-gamma compared with mice receiving IL-12 alone, indicating that IFN-gamma was required for the optimal antitumor efficacy of IL-12. However, several lines of investigation suggest that the antitumor effect of IL-12 is not mediated solely through the induction of IFN-gamma. Exogenous administration of IFN-gamma to Renca tumor-bearing euthymic mice resulted in less antitumor efficacy than that which could be obtained with IL-12. In addition, the antitumor effect of IL-12 was reduced in nude mice compared with euthymic mice, but an approximately 10-fold higher level of serum IFN-gamma was induced in nude than in euthymic mice. Thus, these results indicate that induction of high serum levels of IFN-gamma is not sufficient to mediate the antitumor efficacy of IL-12.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cell Division / physiology
  • Cytokines / immunology
  • Interferon-gamma / blood
  • Interferon-gamma / physiology*
  • Interleukin-12 / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation / immunology
  • Neoplasms, Experimental / immunology
  • Neoplasms, Experimental / therapy*
  • Transfection
  • Tumor Cells, Cultured


  • Antibodies, Monoclonal
  • Cytokines
  • Interleukin-12
  • Interferon-gamma