Enhancement of anti-tumor immunity by post-translational modification of MICA
| Project/Area Number |
17K09405
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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 |
Gastroenterology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Sato Masaya 東京大学, 医学部附属病院, 助教 (30722665)
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| Co-Investigator(Kenkyū-buntansha) |
大塚 基之 東京大学, 医学部附属病院, 講師 (90518945)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 腫瘍免疫 / MICA / 免疫療法 / 切断酵素 / 分泌 / 癌 / 免疫学 |
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| Outline of Final Research Achievements |
A single nucleotide polymorphism at the upstream of MICA gene is associated with the susceptibility of hepatocellualr carcinogenesis. The SNP is associated with the MICA transcriptional levels, which are linked with the activity of anti-tumor immunity. However, the regulation of MICA on the cancer cell surface is not only dependent on the transcriptin but on the post-trasnlational modification, that is, the clevage of MICA from the cell surface into the supernatant. In this study, from the library scree, FAAH inhibitor was identified as an inhibitor of MICA clevage. FAAH inhibitor enhanced TIMP3 expression, which in turn inhibited the MICA shedding. FAAH inhibitor may be useful for the enhancement of anti-tumor immunity through MICA expression on the cancer cell surface.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、肝癌発癌に関与する遺伝子であることが以前に同定されている自然免疫関連分子であるMICAの癌細胞表面からの切断分泌を阻害する化合物を同定できた。
MICA蛋白は癌細胞表面に表出されると "eat-me signal"として作用し、免疫応答を惹起するトリガーとなるが、癌細胞ではMICA蛋白を切断して上清に分泌させてしまう機能がある。本研究によってFAAH阻害剤がMICA蛋白の切断を阻害し、癌細胞表面に表出されたMICA蛋白の量を維持する機能があることが判明した。この知見を応用すれば、癌免疫を増強し、発がん抑制や癌治療の増強につながることが期待される。
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Report
(4 results)
Research Products
(7 results)
