Comprehensive study on IL-27, one of the IL-12 family cytokines, aiming at its clinical application for cancer immunotherapy

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07333
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Tokyo Medical University
• Principal Investigator: Xu Mingli 東京医科大学, 医学部, 客員講師 (80597964)
• Co-Investigator(Kenkyū-buntansha): 善本 隆之 東京医科大学, 医学部, 教授 (80202406)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: IL-27 / がん治療 / 慢性骨髄性白血病 / BCR-ABL

Outline of Final Research Achievements

A number of evidence reveled that IL-27 exerts antitumor effects through multiple mechanism, while it was also reported that IL-27 promotes proliferation of human leukemic cell lines. In addition, we previously demonstrated that IL-27 directly acts on hematopoietic stem cells (HSCs). Herein, we investigated the effects of exogenous IL-27 on the development of chronic myeloid leukemia (CML) using its mouse model, that is established by transferring causative gene BCR-ABL-transduced HSCs into irradiated mice. The results suggest that exogenous IL-27 activated CD8+ T cells and induced apoptosis of BCR-ABL+CML stem cells, which were shown using IL-27-transgenic mice. We also investigated the effects of endogenous IL-27 on the development of CM by transferring WSX-1－BCR-ABL+HSCs into wild-type mice. The results suggest that endogenous IL-27 directly acted on BCR-ABL+CML stem cells and inhibited their proliferation. These results may suggest its inhibitory effect on CML stem cells.

Free Research Field

がん免疫

Academic Significance and Societal Importance of the Research Achievements

がんは、今や国民の半数が罹患し、死因の1/3を占める深刻な病気となっている。今日、免疫チェックポイント阻害薬やキメラ抗原受容体T細胞（CAR-T）療法などのがん免疫療法が注目されているが、治療効果に個人差があることや特定のがんにしか効かないなど、改善が迫られている。そこで、これらのがん免疫療法と、がんワクチン療法、サイトカイン療法などと併用し最善の治療方法を確立することが必要である。サイトカイン療法は、その副作用が大きいことが臨床応用への大きな妨げになっている。IL-12ファミリーサイトカインの1つIL-27は、比較的副作用が少なく強い抗腫瘍活性を示す報告が我々の報告を含め多数ある。