2015 Fiscal Year Final Research Report
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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| 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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| Free Research Field |
腫瘍免疫学
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