| Project/Area Number |
18K07228
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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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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Voon Dominic 金沢大学, がん進展制御研究所, 准教授 (30776878)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | Inflammatory cytokine / tumorigenesis / Tumor immunity / Cancer / Gastric epithelial cells / IL23A |
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| Outline of Final Research Achievements |
The cytokine IL23A is usually produced by leukocytes to promote inflammation. However, we discovered that IL23A is also produced by epithelial cells. Moreover, the epithelial form of IL23A (eIL23A) is different from conventional IL-23. We have purified eIL23A and here we proposed to study its immune functions.
Using mouse leukocytes, we found that eIL23A strongly enhances the effects of canonical IL-23 to cause peritoneal exudate cells (PEC) to produce more IL17A/F, a powerful inducer of inflammation. We observed that when human colorectal cancer cells are activated or carry certain mutations, they will produce eIL23A. This is a definitive evidence for a new form of IL23A. Moreover, when we forced expression of IL-23 in cancer cells, tumor immunity is activated. This is further enhanced when eIL23A is also provided. These data means eIL23A can be used to increase tumor immunity. We believe the findings of this project provide a strong basis to improve immunotherapy in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
慢性炎症はクローン病、乾癬、炎症性腸疾患、リウマチ疾患などの自己免疫疾患の原因である。また、慢性炎症は胃がんなどの難治性疾患の原因であることが知られている。免疫応答で中心的な役割を果たすIL-23の活性制御に関わるeIL23Aの機能を解明により、免疫応答異常に起因する様々な疾患の治療戦略の開発に貢献する。
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