Natural killer cell is a major producer of interferon γ that is critical for the IL-12-induced anti-tumor effect in mice

  • Akio Uemura
  • Tetsuo Takehara
  • Takuya Miyagi
  • Takahiro Suzuki
  • Tomohide Tatsumi
  • Kazuyoshi Ohkawa
  • Tatsuya Kanto
  • Naoki Hiramatsu
  • Norio Hayashi
Original Article


Although the anti-tumor effect of IL-12 is mediated mostly by IFNγ, which cell types most efficiently produce IFNγ and therefore initiate or promote the anti-tumor effect of IL-12 has not been clearly determined. In the present study, we demonstrated hydrodynamic injection of the IL-12 gene led to prolonged IFNγ production, NK-cell activation and complete inhibition of liver metastasis of CT-26 colon cancer cells in wild-type mice, but not in IFNγ knockout mice. NK cells expressed higher levels of STAT4 and upon IL-12 administration displayed stronger STAT4 phosphorylation and IFNγ production than non-NK cells. Adoptive transfer of wild-type NK cells into IFNγ knockout mice restored IL-12-induced IFNγ production, NK-cell activation and anti-tumor effect, whereas transfer of the same number of wild-type non-NK cells did not. In conclusion, NK cells are predominant producers of IFNγ that is critical for IL-12 anti-tumor therapy.


IFNγ Innate immunity Liver tumor IL-12 NK 



We thank Dr. Morihiro Watanabe (Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Development Center) for providing the pCMV-IL-12 plasmid, Dr. Yoichiro Iwakura (University of Tokyo, Institute of Medical Science) for providing GKO mice.

Supplementary material

262_2009_764_MOESM1_ESM.tif (237 kb)
Supplementary material 1 (TIFF 236 kb)


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Akio Uemura
    • 1
  • Tetsuo Takehara
    • 1
  • Takuya Miyagi
    • 1
  • Takahiro Suzuki
    • 1
  • Tomohide Tatsumi
    • 1
  • Kazuyoshi Ohkawa
    • 1
  • Tatsuya Kanto
    • 1
  • Naoki Hiramatsu
    • 1
  • Norio Hayashi
    • 1
  1. 1.Department of Gastroenterology and HepatologyOsaka University Graduate School of MedicineSuita, OsakaJapan

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