Enhancement of antitumor effect of IL-21 by improving cancer microenvironment

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07153
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Ishinomaki Senshu University (2018-2019); Yamagata University (2017)
• Principal Investigator: Nara Hidetoshi 石巻専修大学, 理工学部, 准教授 (00375338)
• Co-Investigator(Kenkyū-buntansha): 浅尾 裕信 山形大学, 医学部, 教授 (80250744) ; 武田 裕司 山形大学, 医学部, 准教授 (90302299)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: インターロイキン２１ / 樹状細胞

Outline of Final Research Achievements

Clinical trials of the treatment of malignant melanoma with IL-21 have been conducted, but to date no significant effect has been obtained. The present study was carried out on the basis that IL-21 may suppress activation of dendritic cells in tumor microenvironment and suppress activation of lymphocytes. Bone marrow-derived dendritic cells were newly found to be differentiated into five stages, and it was found that IL-21 arrests differentiation into mature dendritic cells at the third stage. We have comprehensively analyzed the patterns of genes expressed at this time, and are currently examining its function. In addition, in experiments using mice, it was possible to observe a decrease in immune response due to suppression of dendritic cells due to overexpression of IL-21.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

がんを取り巻く微小な環境では、様々な要因により抗がん剤の影響が阻まれ、十分な効果を発揮できないことがある。IL-21は様々な白血球の活性化を誘導するので、抗腫瘍効果を期待されているが、際立った抗腫瘍効果は得られていない。IL-21は白血球の中で、抗原提示というリンパ球の活性化を担う樹状細胞の活性を抑制することが知られている。よって、その機構を解明することで、新たな治療薬の開発につながるのではないかと考えた。IL-21により、樹状細胞ではいくつかの遺伝子の発現パターンが異なることを見出し、これらを標的としうる可能性が示唆された。