The effect of multi kinase inhibitor in tumor microenvironment and tumor immunity in colorectal cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K16969
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Keio University
• Principal Investigator: Shigeta Kohei 慶應義塾大学, 医学部(信濃町), 助教 (30528790)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 大腸癌 / 腫瘍免疫 / 腫瘍微小環境

Outline of Final Research Achievements

Aim of this study was to assess the correlation between the change of tumor microenvironment and improvement of tumor immunity by multi kinase inhibitor in colorectal cancer (CRC).We developed two different orthotopic model of CRC in mice with CT-26, a microsatelite stable murine CRC cancer cell line. First model was liver implantation model by injecting CT26 directly to the liver. Second model was liver metastasis model by injecting CT26 via splenic vein. In vivo experiment using orthotopic mouse mode was done with regorafenib treatment. We have collected the tumor from these mouse and are now under analysis of distribution of CD8 positive T cells by immunofluorescence. We are now planning to assess the mechanism of activation of tumor immunity by regorafenib treatment with this new mouse model.

Free Research Field

外科学

Academic Significance and Societal Importance of the Research Achievements

新規治療として確立されつつある免疫治療が脚光を浴びているが，免疫治療が有効な大腸癌患者は10%未満とされ，大腸癌における免疫治療のさらなる開発が必要とされている．大腸癌における腫瘍免疫活性化のメカニズムの解明は需要な課題であり，本研究にて確立された人の大腸癌肝転移の発生機序に類似したマウスモデルを確立したことは大きな意義がある．今後はマウスモデルを用いたメカニズムの解明を進めていく．