Study on roles of aryl hydrocarbon receptor (AhR) in tumor microenvironment and estimation of AhR as a therapeutic target for cancer patients
| Project/Area Number |
25430158
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor therapeutics
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
河上 裕 慶應義塾大学, 医学部, 教授 (50161287)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 腫瘍免疫 / 免疫抑制 / AhR / IDO / Kynurenine |
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| Outline of Final Research Achievements |
Aryl hydrocarbon receptor (AhR) was found to be activated in cancer cells and various immune cells in tumor microenvironments. Kynurenine, a tryptophan metabolite by indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO), is involved in activation of AhR in cancer cells. We identified a novel mechanism of immunosuppression through downstream molecules of AhR in cancer cells in tumor microenvironments. Through a comprehensive gene expression analysis and mouse in vivo experiments, we identified several molecules responsible for this immunosuppression observed in tumor with activated IDO-kynurenine-AhR pathway. We also showed that IDO is phosphorylated in human cancer cells and clarified a part of this signal in tumor microenvironment. From our results, targeting AhR in tumor may be a useful strategy for cancer treatment by reversal of immunosuppression in tumor microenvironments.
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Cancer-induced immunosuppressive cascades and their reversal by molecular-targeted therapy.2013
Author(s)
Kawakami Y, Yaguchi T, Sumimoto H, Kudo-Saito C, Tsukamoto N, Iwata-Kajihara T, Nakamura S, Nishio H, Satomi R, Kobayashi A, Tanaka M, Hoon Park J, Kamijuku H, Tsujikawa T, Kawamura N
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Journal Title
Ann. N.Y. Acad. Sci.,
Volume: 1284(1)
Issue: 1
Pages: 80-86
DOI
Related Report
Peer Reviewed
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[Book] Development of personalized combination cancer immunotherapy based on the patients’ immune status in “Inflammation and immunity in cancer ” Eds:Tsukasa Seya, Keiko Udaka, Misako Matsumoto, Noriyuki Sato2015
Author(s)
Kawakami Y, Qian L, Kawamura N, Miyazaki J, Nagumo H, Tsubota K, Kinoshita T, Nakamura K, Ohmura G, Satomi R, Sugiyama J, Nishio H, Hayakawa T, Popivanova B, Nuchsupha S, Liu TH, Kamijuku H, Kudo-Saito C, Tsukamoto N, Sakurai T, Fujita T, Yaguchi T
Publisher
Springer
Related Report
