Anti-cancer immune response to intraperitoneal dissemination of gastric cancer

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16554
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kobe University
• Principal Investigator: Arimoto Akira 神戸大学, 医学部附属病院, 医員 (20778766)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 腹膜播種 / CD8+細胞 / milky spot

Outline of Final Research Achievements

We started to create a peritoneal-dissemination mouse model. We needed a mouse model in which we could observe the disease progression chronologically for the investigation about the mechanism of intraperitoneal immune response failure. We had a hard time to decide an appropriate cell number and timing for analysis because the only way to evaluate the disease progression precisely is to observe the mice directly by opening the abdomen. We finally succeeded in establishing the steady system in which peritoneal dissemination progressed chronologically by injecting MC38, colon cancer cell line, intraperitoneally into BALB/c mice. We evaluated the distribution of T cells in the omentum and peritoneal cavity by flow cytometry. We couldn’t make a detailed analysis of T cells due to the difficulty in stable extraction of them from omentum. In peritoneal dissemination model mice, the proportion of CD8 T cells in the peritoneal cavity showed less change even though the disease progressed.

Free Research Field

癌免疫

Academic Significance and Societal Importance of the Research Achievements

胃癌腹膜播種成立には、大網を含む腹腔内の抗腫瘍免疫の破綻が大きな要因であると考えられる。抗腫瘍免疫破綻のメカニズムを明らかにすることは、新規治療開発の重要な鍵になる。これまで、病勢が進行する時期ごとに評価可能な、消化器癌の細胞株を用いた腹膜播種モデルは確立されていなかった。本研究ではこのモデルを確立し、腹腔内T細胞の評価が可能であった。大網内のT細胞の評価には抽出方法などの改善が必要であるが、今後のモデルマウスを用いた腹膜播種成立の免疫学的メカニズム解明の礎になったと考える。