Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity

K. Watcharanurak, L. Zang, M. Nishikawa, K. Yoshinaga, Yasuko Yamamoto, Y. Takahashi, M. Ando, Kuniaki Saito, Y. Watanabe, Y. Takakura

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Interferon γ (IFN-γ), an anticancer agent, is a strong inducer of indoleamine 2,3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme involved in the induction of tumor immune tolerance. In this study, we investigated the IDO1 expression in organs after IFN-γ gene transfer to mice. IFN-γ gene transfer greatly increased the mRNA expression of IDO1 in many tissues with the highest in the liver. This upregulation was associated with reduced L-tryptophan levels and increased L-kynurenine levels in serum, indicating that IFN-γ gene transfer increased the IDO activity. Then, Lewis lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice were used to investigate the effects of IDO1 on the antitumor activity of IFN-γ. IFN-γ gene transfer significantly retarded the tumor growth in both strains without any significant difference in tumor size between the two groups. By contrast, the IDO1 activity was increased only in the wild-type mice by IFN-γ gene transfer, suggesting that cells other than LLC cells, such as tumor stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken together, these results imply that IFN-γ gene transfer mediated IDO1 upregulation in cells other than LLC cells has hardly any effect on the antitumor activity of IFN-γ.

Original languageEnglish
Pages (from-to)794-801
Number of pages8
JournalGene therapy
Volume21
Issue number9
DOIs
Publication statusPublished - 01-09-2014

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Interferons
Lewis Lung Carcinoma
Genes
Neoplasms
Tryptophan
Up-Regulation
Kynurenine
Immune Tolerance
Stromal Cells
Knockout Mice
Antineoplastic Agents
Messenger RNA
Liver

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Watcharanurak, K. ; Zang, L. ; Nishikawa, M. ; Yoshinaga, K. ; Yamamoto, Yasuko ; Takahashi, Y. ; Ando, M. ; Saito, Kuniaki ; Watanabe, Y. ; Takakura, Y. / Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity. In: Gene therapy. 2014 ; Vol. 21, No. 9. pp. 794-801.
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abstract = "Interferon γ (IFN-γ), an anticancer agent, is a strong inducer of indoleamine 2,3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme involved in the induction of tumor immune tolerance. In this study, we investigated the IDO1 expression in organs after IFN-γ gene transfer to mice. IFN-γ gene transfer greatly increased the mRNA expression of IDO1 in many tissues with the highest in the liver. This upregulation was associated with reduced L-tryptophan levels and increased L-kynurenine levels in serum, indicating that IFN-γ gene transfer increased the IDO activity. Then, Lewis lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice were used to investigate the effects of IDO1 on the antitumor activity of IFN-γ. IFN-γ gene transfer significantly retarded the tumor growth in both strains without any significant difference in tumor size between the two groups. By contrast, the IDO1 activity was increased only in the wild-type mice by IFN-γ gene transfer, suggesting that cells other than LLC cells, such as tumor stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken together, these results imply that IFN-γ gene transfer mediated IDO1 upregulation in cells other than LLC cells has hardly any effect on the antitumor activity of IFN-γ.",
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Watcharanurak, K, Zang, L, Nishikawa, M, Yoshinaga, K, Yamamoto, Y, Takahashi, Y, Ando, M, Saito, K, Watanabe, Y & Takakura, Y 2014, 'Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity', Gene therapy, vol. 21, no. 9, pp. 794-801. https://doi.org/10.1038/gt.2014.54

Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity. / Watcharanurak, K.; Zang, L.; Nishikawa, M.; Yoshinaga, K.; Yamamoto, Yasuko; Takahashi, Y.; Ando, M.; Saito, Kuniaki; Watanabe, Y.; Takakura, Y.

In: Gene therapy, Vol. 21, No. 9, 01.09.2014, p. 794-801.

Research output: Contribution to journalArticle

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AU - Watcharanurak, K.

AU - Zang, L.

AU - Nishikawa, M.

AU - Yoshinaga, K.

AU - Yamamoto, Yasuko

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AU - Ando, M.

AU - Saito, Kuniaki

AU - Watanabe, Y.

AU - Takakura, Y.

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