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タイトル: Effects of upregulated indoleamine 2, 3-dioxygenase 1 by interferon γ gene transfer on interferon γ-mediated antitumor activity.
著者: Watcharanurak, K
Zang, L
Nishikawa, M
Yoshinaga, K
Yamamoto, Y
Takahashi, Y  kyouindb  KAKEN_id
Ando, M
Saito, K
Watanabe, Y
Takakura, Y  kyouindb  KAKEN_id
著者名の別形: 西川, 元也
発行日: 12-Jun-2014
出版者: Nature Publishing Group
誌名: Gene therapy
巻: 21
号: 9
開始ページ: 794
終了ページ: 801
抄録: 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.
著作権等: © 2015 Macmillan Publishers Limited.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/201491
DOI(出版社版): 10.1038/gt.2014.54
PubMed ID: 24919418
出現コレクション:学術雑誌掲載論文等

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