Correlation ofIn VitroandIn VivoEffects of Interferon-γ with the Spontaneous Regression of a Rat Histiocytoma

Abstract

Cytokines trigger activation of different lymphocyte populations, resulting in augmentation of humoral and cell-mediated immunity. We have examined the role of IFN-gamma in mediating AK-5 tumor regression. High levels of circulating IFN-gamma and IL-2 marked the process of regression. Moreover, interaction of immune NK cells with antibody-tagged AK-5 resulted in IFN-gamma secretion, providing in vitro evidence for the involvement of this cytokine. IFN-gamma and IL-2 potentiated the cytolytic activity of naive NK cells, suggesting their role in antitumor activity. Furthermore, pretreatment of immune NK cells with protein tyrosine kinase inhibitor downregulated the IFN-gamma release, suggesting that the secretion of IFN-gamma is phosphorylation dependent. Nonimmune cells could be induced to secrete IFN-gamma when exposed to rIL-12, demonstrating IL-12 dependence in inducing IFN-gamma release. In vivo administration of anti-IFN-gamma inhibited the cytotoxic activity and the process of tumor regression, further substantiating the role of IFN-gamma in regulating the rejection of AK-5 tumor. These observations suggest a definitive role for IFN-gamma in AK-5 regression. This cytokine in concert with IL-2 and IL-12 might aid in designing effective anticancer therapy.