A novel approach in the treatment of intrahepatic cholangiocarcinoma or pancreatic cancer: Focusing on the stromal myofibroblast

• Project/Area Number: 17K10510
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Doshisha University (2018-2019); Kyoto University (2017)
• Principal Investigator: Iwaisako Keiko 同志社大学, 生命医科学部, 教授 (70625300)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 線維化 / 癌免疫 / 肝内胆管癌 / 筋線維芽細胞 / 膵癌 / 癌

Outline of Final Research Achievements

Analysis of clinical specimens of cholangiocarcinoma showed that the higher the fibrosis of the cancerous tissue, the better the prognosis. On the other hand, in the non-tumor of the liver, the higher the fibrosis, the worse the prognosis. There was a correlation between fibroblast infiltration and fibrosis, and the more regulatory T cells infiltrating tumor, the worse the prognosis. For fibrosis, the subtype of collagen, which is a component, was analyzed. The proportion of type III in tumor was higher than that of non-tumor areas, and a correlation was observed between type III non-tumor areas and the infiltration of regulatory T cells into tumor. It was suggested that it may influence prognosis and contribute to the prognosis.

Academic Significance and Societal Importance of the Research Achievements

肝内胆管癌や膵癌は、大変予後が不良な癌で近年の癌免疫療法などの発展による予後改善もなかなか期待できないのが現状である。ほかの癌との違いを、手術で摘出した癌の組織を用いて解析することで、その性質や特徴を詳細に解析し、治療の手掛かりとなる性質を見出すことがこの研究の目的である。我々は、肝内胆管癌に浸潤する免疫細胞の特徴と線維化のについて新たな知見を見出すことができた。この知見を治療法へと展開させたい。

Research Products

• [Journal Article] High-resolution imaging mass spectrometry combined with transcriptomic analysis identified a link between fatty acid composition of phosphatidylinositols and the immune checkpoint pathway at the primary tumour site of breast cancer. (2020)
  • Author(s): Kawashima M, Tokiwa M, Nishimura T, Kawata Y, Sugimoto M, Kataoka TR, Sakurai T, Iwaisako K, Suzuki E, Hagiwara M, Harris AL, Toi M.
  • Journal Title: Br J Cancer. Volume: 122 Issue: 2 Pages: 245-257
  • DOI: 10.1038/s41416-019-0662-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Tyrosine kinase inhibitor imatinib augments tumor immunity by depleting effector regulatory T cells (2020)
  • Author(s): Tanaka A, Katayama N, et al (他21名, 21番目)
  • Journal Title: Journal of Experimental Medicine Volume: 217 Issue: 2
  • DOI: 10.1084/jem.20191009
  • Peer Reviewed / Open Access
• [Journal Article] Activated hepatic stellate cells and portal fibroblasts contribute to cholestatic liver fibrosis in MDR2 knockout mice. (2019)
  • Author(s): Nishio T, Hu R, Koyama Y, Liang S, Rosenthal SB, Yamamoto G, Karin D, Baglieri J, Ma HY, Xu J, Liu X, Dhar D, Iwaisako K, Taura K, Brenner DA, Kisseleva T.
  • Journal Title: J Hepatol. Volume: 71 Issue: 3 Pages: 573-585
  • DOI: 10.1016/j.jhep.2019.04.012
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Serum nardilysin, a surrogate marker for epithelial-mesenchymal transition, predicts prognosis of intrahepatic cholangiocarcinoma after surgical resection (2019)
  • Author(s): Yoh T, Hatano E, Kasai Y, Fujii H, Nishi K, Toriguchi K, Sueoka H, Ohno M, Seo S, Iwaisako K, Taura K, Yamaguchi R, Kurokawa M, Fujimoto J, Kimura T, Uemoto S, and Nishi E.
  • Journal Title: Clin Cancer Res. Volume: 25(2) Issue: 2 Pages: 619-629
  • DOI: 10.1158/1078-0432.ccr-18-0124
  • Peer Reviewed / Open Access
• [Journal Article] Preoperative metabolic tumor volume of intrahepatic cholangiocarcinoma measured by 18F-FDG-PET is associated with the KRAS mutation status and prognosis. (2018)
  • Author(s): Ikeno Y, Seo S, Iwaisako K, Yoh T, Nakamoto Y, Fuji H, Taura K, Okajima H, Kaido T, Sakaguchi S, Uemoto S
  • Journal Title: J Transl Med. Volume: 16 Issue: 1 Pages: 95-95
  • DOI: 10.1186/s12967-018-1475-x
  • Peer Reviewed / Open Access
• [Presentation] Liver fibrosis and origin of myofibroblasts (2020)
  • Author(s): Keiko Iwaisako
  • Organizer: the 39th Japanese Society for Biomedical Research on Alcohol
  • Int'l Joint Research / Invited
• [Presentation] FOXP3は肝内胆管癌における予後不良因子である (2019)
  • Author(s): 塚本 祥子、祝迫 惠子
  • Organizer: 第78回 日本癌学会総会
• [Presentation] Effort toward clinical application of cancer immunotherapy against intrahepatic cholangiocarcinoma. (2018)
  • Author(s): Hiroaki Fuji, Keiko Iwaisako, Masataka Asagiri, Satoru Seo, Kojiro Taura, Toshimi Kaido, Hideaki Okajima and Shinji Uemoto
  • Organizer: 8th International Forum of Liver Surgery
  • Int'l Joint Research
• [Presentation] The involvement of regulatory T cells for intrahepatic cholangiocarcinoma in cancer immunity. (2018)
  • Author(s): Hiroaki Fuji, Keiko Iwaisako, Masataka Asagiri, Satoru Seo, Kojiro Taura, Toshimi Kaido, Hideaki Okajima and Shinji Uemoto
  • Organizer: The 53rd Congress of the European Society for Surgical Research
  • Int'l Joint Research
• [Presentation] 肝内胆管癌に対する癌免疫療法の臨床応用にむけた取り組み (2018)
  • Author(s): 藤 浩明、祝迫 惠子、朝霧 成挙、瀬尾 智、田浦 康二朗、海道 利実、岡島 英明、坂口 教子、坂口 志文、上本 伸二
  • Organizer: 第118回日本外科学会定期学術集会