| 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)
|
|---|
| 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.
|
