Novel radioimmunotherapy for rectal cancer based on the tumor metabolism

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09225
• 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: Jichi Medical University
• Principal Investigator: Koinuma Koji 自治医科大学, 医学部, 准教授 (20382905)
• Co-Investigator(Kenkyū-buntansha): 北山 丈二 自治医科大学, 医学部, 教授 (20251308) ; 堀江 久永 自治医科大学, 医学部, 教授 (20316532) ; 田原 真紀子 自治医科大学, 医学部, 助教 (30406102) ; 井上 賢之 自治医科大学, 医学部, 講師 (80375279)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 直腸癌 / 免疫放射線療法 / Abscopal Effect / 肺転移 / メトホルミン

Outline of Final Research Achievements

We used a a hyperlung metastasis strain LuM1 and examined the efficacy of radiotherapy in combination with metformin. The primary lesion was significantly reduced by irradiation, but no effect was observed on lung metastases. However, the combined use of metformin with radiation therapy also showed a reduction effect on lung metastases in distant lesions. Flow cytometry of spleen cells and immunohistochemical staining of lung metastases revealed that IFN-g-producing ability of T cells in spleen cells, NK cells, and G-MDSC were involved in this mechanism. Was there. In lung metastasis, it was possible to show that NK cells and G-MDSC are effective in suppressing lung metastasis. Metformin effectively enhances local and abscopal effects of radiation therapy though the activation of cell-mediated immunity and might be clinically useful as neoadjuvant treatment for patients with locally advanced colorectal cancer.

Free Research Field

腫瘍外科学

Academic Significance and Societal Importance of the Research Achievements

大腸癌は罹患数、死亡率ともに上位を占めている疾患の一つである。遠隔転移がある場合、きわめて予後が不良である。術前の放射線療法が局所再発率の低下につながるようになったが、遠隔転移に対する効果は認められていない。糖尿病治療薬メトホルミンの抗腫瘍効果が注目されており、宿主の免疫応答に関与することが報告されている。本研究ではメトホルミン併用による免疫放射線療法の効果とその機序の一因を示す事が出来た重要な研究結果である。