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

Expression of a dominant negative mutant IFN gamma R1 in murine SCK and K1735 tumor cells rendered them relatively unresponsive to IFN gamma in vitro and more tumorigenic and less responsive to IL-12 therapy in vivo. IL-12 induced histologic evidence of ischemic damage only in IFN gamma-responsive tumors, and in vivo Matrigel vascularization assays revealed that while IFN gamma-responsive and -unresponsive tumor cells induced angiogenesis equally well, IL-12 and its downstream mediator IFN gamma 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 IFN gamma inhibit tumor growth by inducing tumor cells to generate antiangiogenic activity.