Analyses for expression and function of the sulfotransferase SULT2B1b

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H00983
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Kyushu University
• Principal Investigator: Fukui Yoshinori 九州大学, 生体防御医学研究所, 教授 (60243961)
• Co-Investigator(Kenkyū-buntansha): 宇留野 武人 九州大学, 生体防御医学研究所, 准教授 (80532093)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 遺伝子発現 / 生理活性脂質 / 生体機能

Outline of Final Research Achievements

DOCK2 is a Rac activator critical for migration and activation of lymphocytes and its mutations cause severe immunodeficiency in humans. We recently found that cholesterol sulfate (CS), a lipid product of the sulfotransferase SULT2B1b, acts as a DOCK2 inhibitor and prevents tissue infiltration by effector T cells. In this study, we analyzed expression and function of CS, mainly focusing on cancer tissues and obtained the following results. 1) CS is abundantly produced in certain types of human cancers such as colon cancers. 2) CS-producing cancer cells exhibited resistance to cancer-specific T cell transfer and immune checkpoint blockade. Then, we screened chemical library and identified candidate compounds of SULT2B1b inhibitors.

Free Research Field

機能生物化学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、新しいがんの免疫回避メカニズムの理解につながるものであり、その学術的意義は大きい。また現在、免疫チェックポイント阻害やCAR-T細胞療法に加え、iPS細胞を用いてがん特異的T細胞を増幅・移入する試みもなされているが、こららの免疫療法が効果を発揮するには、T細胞ががん組織に浸潤することが必要である。本研究の成果により、臨床応用可能なSULT2B1b阻害剤が開発され、がんの免疫回避環境を破壊することができれば、その社会的、経済的インパクトは大きいと期待される。