IFN-γ Mediates the Antitumor Effects of Radiation Therapy in a Murine Colon Tumor

Cancer treatments using ionizing radiation (IR) therapy are thought to act primarily through the induction of tumor cell damage at a molecular level. However, a new concept has recently emerged, suggesting that the immune system is required for effective IR therapy. Our work here has identified interferon gamma (IFN-gamma) as an essential cytokine for the efficacy of IR therapy. Local IR (15 Gy) to mice bearing Colon38, a colon adenocarcinoma, decreases tumor burden in wild-type animals. Interestingly, IR therapy had no effect on tumor burden in IFN gamma KO mice. We further determined that intratumoral Levels of IFN-gamma increased 2 days following IR, which directly correlated with a decrease in tumor burden that was not a result of direct cytotoxic effects of IFN-gamma on tumor cells. T cells from IR-treated tumors exhibited a far greater capacity to Lyse tumor cells in a Cr-51 release assay, a process that was dependent on IFN-gamma. CD8(+) T cells were the predominant producers of IFN-gamma, as demonstrated by IFN-gamma intracellular staining and studies in IFN-gamma reporter mice. Elimination of CD8(+) T cells by antibody treatment reduced the intratumoral levels of IFN-gamma by over 90%. More importantly, elimination of CD8(+) T cells completely abrogated the effects of radiation therapy. Our data suggest that IFN-gamma plays a pivotal role in mediating the antitumor effects of IR therapy.