Correlation of in vitro and in vivo effects of interferon-gamma with the spontaneous regression of a rat histiocytoma.
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.
Kausalya
S
S
Centre for Cellular and Molecular Biology, Hyderabad, India.
Varalakshmi
C
C
Khar
A
A
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D009365:Neoplasm Regression, Spontaneous; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D007376:Interleukin-2; D007371:Interferon-gamma