Potential for IL-18 immunotherapy targeting tumor-associated macrophages

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K09124
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Yamada Naoko 兵庫医科大学, 医学部, 講師 (10319858)
• Co-Investigator(Kenkyū-buntansha): 中正 恵二 兵庫医科大学, 医学部, 教授 (00217712) ; 山根木 康嗣 兵庫医科大学, 医学部, 講師 (00434944) ; 西浦 弘志 兵庫医科大学, 医学部, 助教 (90284760)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: IL-18 / 腫瘍関連マクロファージ / がん微小環境 / M1 / M2

Outline of Final Research Achievements

Interleukin 18 (IL-18) was discovered in our college, and its physiological significance was investigated by researchers around the world. It was shown that IL-18 plays an important role in biological functions such as the maintenance of homeostasis. Our studies have shown that IL-18 has anti-tumor activity against cancer. The activity is mainly mediated by T cells and NK cells. In this study, we investigate the effect of IL-18 on macrophages, especially on tumor-associated macrophages. We established a system to induce differentiation of M1 and M2 macrophages for in vitro analysis and examined the characteristics of M1 and M2 under different culture conditions. We found that IL-18 has a suppressive effect on the expression of various M2 markers although IL-18 did not affect the induction of M1 and M2 differentiation.

Free Research Field

腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

我々はIL-18の抗腫瘍効果に関する研究を行ってきた。これまでにT細胞、NK細胞を介する以外の作用で抗腫瘍効果を発揮することが分かっているが、そのメカニズムは分かっていない。腫瘍内には腫瘍関連マクロファージ（TAM）が存在し、M2タイプのTAMが腫瘍促進性に働くことが分かっている。本研究ではIL-18は直接M1, M2の分化誘導には影響していなかったが、M2に作用し抑制していることが明らかとなった。このことによりIL-18の新たな生理的意義が明らかにされ、新たな視点によるがん治療法の開発に貢献できると考える。