Studies of treatment and carcinogenesis for intrahepatic cholangiocarcinoma by genomic and immunological analysis
Project/Area Number |
17K10674
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Digestive surgery
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Research Institution | Osaka City University |
Principal Investigator |
Kubo Shoji 大阪市立大学, 大学院医学研究科, 准教授 (80221224)
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Co-Investigator(Kenkyū-buntansha) |
竹村 茂一 大阪市立大学, 大学院医学研究科, 講師 (00322363)
土原 一哉 国立研究開発法人国立がん研究センター, 先端医療開発センター, 分野長 (00415514)
佐藤 保則 金沢大学, 医学系, 准教授 (30324073)
田中 肖吾 大阪市立大学, 大学院医学研究科, 講師 (50382114)
冨樫 庸介 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (80758326)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 職業性胆管癌 / 化学発癌 / DNA傷害 / 多中心性発癌 / 癌免疫応答 / 免疫チェックポイント阻害剤 / 多中性発癌 / 慢性胆管傷害 / DNA損傷 / 肝内胆管癌 / 遺伝子変異 / 免疫学 |
Outline of Final Research Achievements |
The gene analysis of occupational cholangiocarcinoma revealed a high mutation burden and a unique trinucleotide mutation signature and multicentric carcinogenesis. By immunohistochemical analysis, cholangiocarcinoma cells and massive invasion of immune cells including cytotoxic T cells were positive for PD-1 and PD-L1. The combined positive score was 10% to 90%, which was extremely higher than non-occupational cholangiocarcinoma. These findings indicate that occupational cholangiocarcinoma has characteristic immune response such as a high mutation burden, cancer immune cells positive for PD-1 and PD-L1, massive invasion of immune cells, which suggests the usefulness of immune checkpoint inhibitors.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は職業性胆管癌と通常の胆管癌における遺伝子解析および病理学的検討を行った結果、通常の胆管癌に比較し、職業性胆管癌では著明な遺伝子変異、著明なPD-1やPD-L1陽性を示す癌細胞や浸潤免疫細胞、著明な細胞障害性T細胞を含む免疫細胞浸潤など特徴的な免疫応答が惹起されていた。このことは、胆管癌発癌において特異な免疫応答が惹起され、その特徴を活用した治療法が存在することが判明した。すなわち本研究によって胆管癌の発癌メカニズムやそれに伴う病態の解明と、新たな治療法の開発に結び付けることができた。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] The clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography in patients with occupational cholangiocarcinoma2018
Author(s)
Kinoshita M, Takemura S, Tanaka S, Shinkawa H, Hamano G, Ito T, Koda M, Aota T, Nakanuma Y, Sato S, Nakamori S, Arimoto A, Yamamoto T, Toyokawa H, Kubo S
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Journal Title
Asian Pacific Journal of Cancer Prevention
Volume: 19
Pages: 1753-1759
Related Report
Peer Reviewed / Open Access
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[Journal Article] Long-term outcomes after biliary diversion operation for pancreaticobiliary maljunction in adult patients2018
Author(s)
Aota T, Kubo S, Takemura S, Tanaka S, Amano R, Kimura K, Yamazoe S, Shinkawa H, Ohira G, Shibata T, Horiike M
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Journal Title
Annals of Gastroenterological Surgery
Volume: 3
Issue: 2
Pages: 217-223
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Indications for laparoscopic liver resection of mass-forming intrahepatic cholangiocarcinoma2018
Author(s)
Kinoshita M, Kanazawa A, Takemura S, Tanaka S, Kodai S, Shinkawa H, Shimizu S, Murata A, Nishio K, Hamano G, Ito T, Tsukamoto T, Kubo S
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Journal Title
Asian Journal of Endoscopic Surgery
Volume: -
Issue: 1
Pages: 46-58
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The PD-1/PD-L1 may be aberrantly activated in occupational cholangiocarcinoma2016
Author(s)
Sato Y, Kinoshita M, Takemura S, Tanaka S, Hamano G, Nakamori S, Fujikawa M, Sugawara Y, Yamamoto T, Arimoto A, Yamamura M, Sasaki M, Harada K, Nakanuma Y, Kubo S
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Journal Title
Pathology International
Volume: 67
Issue: 3
Pages: 163-170
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Validation of IWATE criteria for laparoscopic liver resection2019
Author(s)
Tanaka S, Kawaguchi Y, Kubo S, Kanazawa A, Takeda Y, Hirokawa F, Nitta H, Nakajima T, Kaizu T, M. Kaibori M, Kojima T, Otsuka Y, Fuks D, Hasegawa K, Kokudo N, Kaneko H, Gayet B, Wakabayashi G
Organizer
The 2nd World Congress of the International Laparoscopic Liver Resection Society
Related Report
Int'l Joint Research
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[Presentation] Comparison of three-level procedure-based classification for laparoscopic liver resection with index-based IWATE criteria2019
Author(s)
Kawaguchi Y, Tanaka S, Fuks D, Kanazawa A, Takeda Y, Hirokawa F, Nitta H, Nakajima T, Kaizu T, Kaibori M, Kojima T, Otsuka Y, Kubo S, Hasegawa K, Kokudo N, Kaneko H, Wakabayashi G, Gayet B
Organizer
The 2nd World Congress of the International Laparoscopic Liver Resection Society
Related Report
Int'l Joint Research
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[Presentation] Surgical outcomes following open or laparoscopic hepatic resection for hepatocellular carcinoma: Case-matched study with propensity score matching2019
Author(s)
Shinkawa H, Tanaka S, Takemura S, Amano R, Kimura K, Yamazoe S, Ohira G, Nishioka T, Ito T, Miyazaki T, Ishihara A, Kubo S
Organizer
The 2nd World Congress of the International Laparoscopic Liver Resection Society
Related Report
Int'l Joint Research
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