Antitumor activity and modified immunoregulation associated with IFN-gamma treatment of RG2 gliomas

Interferon-gamma (IFN-gamma) is a key cytokine that upregulates molecules that participate in the processing and presentation of antigen, and effectively induces various immune regulatory factors. IFN-gamma also has cytotoxic or antitumor activities against some tumors in humans as well as animals. In this study, we evaluated the antitumor activity of recombinant rat IFN-gamma (rrIFN-gamma) on RG2 gliomas, and its immunological effect on tumor sites.

Rats with RG2 gliomas were intracarotidly treated by rrIFN-gamma with or without RMP-7, which has been reported to selectively increase the transport of cytokines to tumor tissue. To evaluate its immunological effect on tumor sites, an immunohistochemical study was performed using monoclonal antibodies against MHC class-1, CD8 and ED2 antigens after rrIFN-gamma treatment.

Intracarotid treatment with high rrIFN-gamma (2.4 x 10(5) U/kg) significantly increased survival (p < 0.02), however, the combined use of RMP-7 and rrIFN-gamma did not result in a further increase. Although the immunohistochemical study showed no clear increase in the staining of MHC class-1 or CD8 antigens on tumors following rrIFN-gamma treatment, immunostaining for ED2 antigen, which is known to be expressed on perivascular cells with MHC class-2 antigen, revealed a clear increase in the number of infiltrating positive cells within the tumors.

Intracarotid rrIFN-gamma treatment can increase survival in rat glioma models through a mechanism in which antigen presentation is enhanced, and such effects are not always further increased by combination with RMP-7.