2018 Fiscal Year Final Research Report
Elucidation of BCG resistance mechanism by comprehensive analysis of immune environment and gene mutation in bladder cancer
| Project/Area Number |
16K10994
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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 | University of Tsukuba |
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Principal Investigator |
Joraku Akira 筑波大学, 医学医療系, 客員研究員 (60436277)
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| Co-Investigator(Kenkyū-buntansha) |
宮崎 淳 国際医療福祉大学, 医学部, 主任教授 (10550246)
木村 友和 筑波大学, 医学医療系, 講師 (10633191)
西山 博之 筑波大学, 医学医療系, 教授 (20324642)
小島 崇宏 筑波大学, 医学医療系, 講師 (40626892)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | BCG / PD-L1 |
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| Outline of Final Research Achievements |
To elucidate the relationship between somatic mutations and tumor immune environment in bladder cancer, we analyzed bladder cancer tissues of 103 bladder cancer patients. We compared the relationship tumor characteristics with tumor immune environment. There were less CD8 positive infiltrating cells in FGFR3 mutation than in FGFR3 wild cases. There were more CD8 positive cells in TP53 mutation than TP53 wild cases.
To clarify the immune environment involved in BCG resistance, PD-L1 expression was evaluated using 53 cases of BCG resistance. There was no difference between before and after BCG treatment with regard to PD-L1 expression in tumor cells. On the other hand, in cases before BCG treatment, PD-L1 expression in tumor cells is enhanced, suggesting that PD-L1 expression in tumor cells may contribute to the mechanism of BCG resistance. PD-L1 expression in tumor tissues was elevated after BCG treatment, suggesting a relationship with BCG-induced inflammation.
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| Free Research Field |
泌尿器悪性腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
非筋層浸潤性膀胱癌に対するBCG膀胱内注入療法は再発や進展の抑制に有効であるが、BCG抵抗性に対しては膀胱全摘等の侵襲的治療が余儀なくされている。BCG抵抗性を事前に予測することはできず、抵抗性の機序も明らかになっていない。本研究ではBCG抵抗性症例のPD-L1発現を検証し、BCG抵抗性の機序の一つとして膀胱癌のPD-L1発現の関与が示唆された。また膀胱癌における体細胞変異と腫瘍免疫環境との関連着目し、膀胱癌においてFGFR3遺伝子に変異を有する症例は腫瘍細胞への免疫細胞浸潤が少なくTP53遺伝子に変異を有する患者症例では腫瘍細胞への免疫細胞浸潤が多いことがわかった。
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