2020 Fiscal Year Final Research Report

Establishment of metastasis control method by elucidation of immune response evasion mechanism of blood circulating cancer stem cells in esophageal cancer

Research Project

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Project/Area Number	18H02878
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	University of Toyama
Principal Investigator	FUJII Tsutomu 富山大学, 学術研究部医学系, 教授 (60566967)
Co-Investigator(Kenkyū-buntansha)	大永崇富山県産業技術研究開発センター, その他部局等, 副主幹研究員 (10416133) 奥村知之富山大学, 学術研究部医学系, 講師 (10533523) 吉岡伊作富山大学, 学術研究部医学系, 特命講師 (30436430) 平野勝久富山大学, 学術研究部医学系, 助教 (40819405) 渋谷和人富山大学, 学術研究部医学系, 助教 (50636248) 渡辺徹富山大学, 学術研究部医学系, 助教 (50779486)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	静止期癌幹細胞 / 血液循環癌幹細胞 / 食道扁平上皮癌 / CTC / T細胞受容体遺伝子 / 食道癌
Outline of Final Research Achievements	Throughout the study period, we identified and isolated quiescent cancer stem cells using resected esophageal squamous cell carcinoma specimens. Since it was not possible to identify cancer stem cells within the first year, the culture conditions for cells collected from immunodeficient mouse subcutaneous transplantation models were re-established in the next year, and good results were obtained. The process of collecting stromal cells such as cancer stem cells and tumor infiltrating lymphocytes directly from cancer tissues without cancer cell culture, and the replacement of CTC detection with EpCAM for epithelial markers such as EGFR and PLS3 that are not changed by EMT, enabled us to isolate cells and detect cell fractions with higher cancer stem cell traits. In cases of resected specimens, p75NTR expression was detected by flow cytometry in preoperative peripheral blood.
Free Research Field	消化器外科学
Academic Significance and Societal Importance of the Research Achievements	血液循環癌幹細胞における特異的免疫回避機構を解析することで、遠隔転移を制御する新たな免疫治療標的を探索する基礎研究である。さらに、リキッドバイオプシーとしての末梢血液循環癌幹細胞検出法を開発することで食道扁平上皮癌に対するテーラーメイド免疫療法の確立および臨床応用が可能となる。難治である食道扁平上皮癌の遠隔転移を制御することで治療を進歩させることができる。