| Project/Area Number |
16K11018
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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 |
Urology
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
Ishibashi Kei 福島県立医科大学, 医学部, 准教授 (90347211)
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| Co-Investigator(Kenkyū-buntansha) |
柳田 知彦 福島県立医科大学, 医学部, 講師 (20363765)
羽賀 宣博 福島県立医科大学, 医学部, 講師 (50586617)
小島 祥敬 福島県立医科大学, 医学部, 教授 (60305539)
相川 健 福島県立医科大学, 医学部, 准教授 (80295419)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 腎癌 / TRAIL / PD-L1 / サイトカイン |
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| Outline of Final Research Achievements |
We investigated the effect of suppressor of cytokine signaling (SOCS) 3 on the expression of TRAIL receptors (DR4) and on TRAIL sensitivity in renal cell carcinoma (RCC) cells. DR4 expression was up-regulated by IFN-alpha stimulation in RCC cells. 786-O cells were resistant to TRAIL and showed higher SOC3 expression. ACHN cells showed higher DR4 expression and lower SOCS3 expression. Suppression of SOCS3 up-regulated DR4 expression and enhanced the TRAIL sensitivity in 786-O cells. In ACHN cells, DR4 expression was down-regulated by transfection with pCI-SOCS3, and the cells became resistant to TRAIL. PD-L1 expression was up-regulated by IFN-alpha, gamma and IL-2. PD-L1 expression was not changed by SOCS3 siRNA transfection. Our results indicate that IFN and SOCS3 regulate DR4 but not PD-L1expression in RCC cells.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、腎癌に対する治療として免疫チェックポイント阻害剤が注目されている。特に抗PD-1およびPD-L1抗体は、高い反応が認められているがその効果は十分とは言えない。本研究では癌免疫の一翼を担うNK細胞に発現するTRAIL受容体DR4発現メカニズムのひとつとその解決法を解明した。PD-L１発現メカニズムについてはさらなる研究が待たれるが、本研究の結果を含め、癌免疫療法に対する抵抗性の対処法が明らかとなる事は、癌治療のさらなる発展が期待でき社会的意義が大きい。
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