IFN-γ mediates the antitumor effects of radiation therapy in a murine colon tumor

Am J Pathol. 2013 Jun;182(6):2345-54. doi: 10.1016/j.ajpath.2013.02.041. Epub 2013 Apr 12.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / radiotherapy*
  • Cytotoxicity, Immunologic / radiation effects
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / deficiency
  • Interferon-gamma / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Transplantation


  • Interferon-gamma