IFNγ mediates the antitumor effects of radiation therapy (165.34)

Abstract

Abstract Radiation (IR) therapy has long been an effective cancer treatment acting primarily through the induction of tumor cell damage at a molecular level. However, a new concept is emerging suggesting that the immune system plays a pivotal role in determining the effectiveness of IR therapy. We have previously demonstrated that IR therapy promotes antitumor immunity through the release of tumor antigens and induction of a pro-inflammatory tumor microenvironment. Our work here has identified IFNγ as an essential cytokine which mediates the efficacy of IR therapy. Local IR (15Gy) to mice bearing colon38, a colon adenocarcinoma, resulted in decreased tumor burden in wild type animals. Interestingly, IR therapy had no effect on tumor burden in IFNγKO mice. We further determined that intratumoral (i.t.) levels of IFNγ spiked two days following IR which directly correlated with a decrease in tumor burden that was not a result of direct cytotoxic effects of IFNγ on tumor cells. CD8+ T cells and NK cells were the predominant producers of IFNγ, however both radiosensitive populations were depleted by IR; a paradox not yet completely understood. IR treated tumors could be further divided into responders and non-responders. Responders were shown to possess higher IFNγ levels, and i.t. treatment with IFNγ further enhanced the effectiveness of IR therapy. These data suggest that IFNγ may play a pivotal role in mediating the antitumor effects of IR therapy.