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

Background: 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 h as cytotoxic or antitumor activities against some tumors ii? humans as well as animals. In this study, we evaluated the antitumor activity of recombin ant rat IFN-gamma (rrIFN-gamma) on RG2 gliomas, and its immunological effec t on tremor sires, Materials and methods: Rats with RG2 gliomas were intrac arotidly treated by rrIFN-gamma with or without RMP-7, which has been repor ted to selectively increase the transport of cytokines to tumor tissue. To evaluate its immunological effect on tumor sites, an immunohistochemical st udy was performed rising monoclonal antibodies against MHC class-1, CD8 and ED2 antigens after rrIFN-gamma treatment. Results: Intracarotid treatment with high rrIFN-gamma (2.4x10(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 followin g rrIFN-gamma treatment, immunostaining for ED2 antigen, which is known to be expressed on perivascular cells with MHC class-2 antigen, revealed a cle ar increase in the number of infiltrating positive cells within the tumors. Conclusion: Intracarotid rrIFN-gamma treatment can increase survival in ra t glioma n models through a mechanism in which antigen presentation is enha nced and such effects are not always further increased by combination with RMP-7.