Immune-inflammatory mechanisms in IFN gamma-mediated anti-tumor activity

IFN gamma is a functionally pleiotropic cytokine which shows considerable p otency in promoting anti-tumor functions in vivo. Despite limited efficacy when delivered systemically either to experimental animals or patients, IFN gamma appears to play an important and perhaps critical role in directing the development of immune-mediated tumor destruction when expressed within the tumor bed. This has been demonstrated both by use of tumor cells transd uced to express IFN gamma and by the use of IL-12 which is able, at least i s murine models, to promote an IFN gamma-dependent, T cell mediated antitum or response. Recent studies indicate that the therapeutic efficacy of IFN g amma in tumor models depends critically upon the ability of the tumor cells themselves to respond to IFN gamma. Though IFN gamma is able to induce ant i-viral activity and has direct anti-proliferative effects on some tumor ce ll lines, immunomodulatory function also appears to be an important compone nt of its anti-tumor action. This is mediated through the action of several different classes of IFN gamma-inducible gene expression which control ant igen processing and presentation, leukocyte trafficking; and indirect tumor cytotoxicity.