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

Christina M. Coughlin, Kevin E. Salhany, Michael S. Gee, Denise C. LaTemple, Serguei Kotenko, Xiao Jing Ma, Giorgia Gri, Maria Wysocka, Ji Eun Kim, Li Liu, Fang Liao, Joshua M. Farber, Sidney Pestka, Giorgio Trinchieri, William M.F. Lee

Research output: Contribution to journalArticlepeer-review

296 Scopus citations

Abstract

Expression of a dominant negative mutant IFNγR1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFNγ in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFNγ-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFNγ-responsive and -unresponsive tumor cells induced anglogenesis equally well, IL-12 and its downstream mediator IFNγ, 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 IFNγ, inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalImmunity
Volume9
Issue number1
DOIs
StatePublished - Jul 1998

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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