2023 Fiscal Year Final Research Report

New chemoradiation-immunotherapy combination therapy for rectal cancer using Wnt signaling

Research Project

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Project/Area Number	21K08798
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 55020:Digestive surgery-related
Research Institution	Kobe University
Principal Investigator	Koide Takahiro 神戸大学, 医学研究科, 医学研究員 (40795415)
Co-Investigator(Kenkyū-buntansha)	西田満福島県立医科大学, 医学部, 教授 (30379359) 松田武神戸大学, 医学研究科, 特命准教授 (30782734) 掛地吉弘神戸大学, 医学研究科, 教授 (80284488) 山下公大神戸大学, 医学部附属病院, 特命准教授 (80535427)
Project Period (FY)	2021-04-01 – 2024-03-31
Keywords	直腸癌 / 化学放射線 / Wnt / 免疫
Outline of Final Research Achievements	In NACRT rectal cancer, β-catenin expression intensity was significantly correlated with response rate and overall survival rate. Furthermore,CD8+ infiltration and response rate also showed a high correlation, with the high CD8+ infiltration group having a significantly better recurrence-free survival rate. Furthermore, in a mouse model transplanted with a cultured colon cancer cell line, it exhibited radiation dose-dependent antitumor effects, and CD8+ T cells were induced in a radiation dose-dependent manner. In this model, the main component of the antitumor effect was CD8+ T cells that existed within the tumor before irradiation. These results indicate that Wnt signal inhibition to promote lymphocyte infiltration is required before radiation. In the future, we plan to optimize protocols for Wnt signal inhibitors and radiotherapy in mouse models.
Free Research Field	消化器外科
Academic Significance and Societal Importance of the Research Achievements	直腸癌は難治性であり、生命予後不良なだけでなく、人工肛門など生活の質が大幅に低下する可能性があり、その治療成績の向上は重要な課題である。治療成績向上を目指して術前化学放射線療法が行われるが、その成績は十分とはいえず、更なる改善が望まれる。本研究成果により、化学放射線の治療効果には腫瘍内に存在する免疫細胞の浸潤が大きな役割を果たしており、免疫細胞浸潤を抑制するWntシグナルを阻害することで、Wnt阻害剤と免疫複合療法など、新たな治療方法につながる可能性が示された。