Tumor cell responses to IFNgamma affect tumorigenicity and response to IL-12 therapy and antiangiogenesis

Immunity. 1998 Jul;9(1):25-34. doi: 10.1016/s1074-7613(00)80585-3.


Expression of a dominant negative mutant IFNgammaR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNgamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNgamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNgamma-responsive and -unresponsive tumor cells induced angiogenesis equally well, IL-12 and its downstream mediator IFNgamma only inhibited angiogenesis induced by the responsive cells. IL-12 induced angiogenesis inhibitory activity in the responsive cells, which may be attributable to production of the chemokine IP-10. Thus, IL-12 and IFNgamma inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Gene Expression
  • Interferon-gamma / pharmacology*
  • Interleukin-12 / therapeutic use*
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Melanoma, Experimental / drug therapy*
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C3H
  • Mutagenesis
  • Neovascularization, Pathologic*
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Recombinant Proteins
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Receptors, Interferon
  • Recombinant Proteins
  • interferon gamma receptor
  • Interleukin-12
  • Interferon-gamma