title: IFN-γ mediates the antitumor effects of radiation therapy in a murine colon tumor.
abstract: 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-γ) 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 IFNγKO mice. We further determined that intratumoral levels of IFN-γ 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-γ on tumor cells. T cells from IR-treated tumors exhibited a far greater capacity to lyse tumor cells in a (51)Cr release assay, a process that was dependent on IFN-γ. CD8(+) T cells were the predominant producers of IFN-γ, as demonstrated by IFN-γ intracellular staining and studies in IFN-γ reporter mice. Elimination of CD8(+) T cells by antibody treatment reduced the intratumoral levels of IFN-γ by over 90%. More importantly, elimination of CD8(+) T cells completely abrogated the effects of radiation therapy. Our data suggest that IFN-γ plays a pivotal role in mediating the antitumor effects of IR therapy.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, New York 14642, USA. scott_gerber@urmc.rochester.edu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
authors.forename: Abigail L
authors.initials: AL
authors.lastname: Sedlacek
authors.forename: Kyle R
authors.initials: KR
authors.lastname: Cron
authors.forename: Shawn P
authors.initials: SP
authors.lastname: Murphy
authors.forename: John G
authors.initials: JG
authors.lastname: Frelinger
authors.forename: Edith M
authors.initials: EM
authors.lastname: Lord
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D003602:Cytotoxicity, Immunologic / Q000528:radiation effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation
chemical_list: D007371:Interferon-gamma