Searching for immune checkpoint molecules regulated by an RNA-binding protein HuR

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22533
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: KAWAI TARO 奈良先端科学技術大学院大学, 先端科学技術研究科, 教授 (50456935)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 自然免疫 / 腫瘍 / 樹状細胞 / RNA結合タンパク質

Outline of Final Research Achievements

We focused on the immune evasion mechanism of cancer cells to search for new genes and to elucidate their mechanisms of action. We found that the infiltration of killer T cells into the tumor tissue was significantly increased and the tumor volume was decreased in mice transplanted with LLC cells lacking HuR, a mRNA-binding protein that medites its stability. By searching for HuR-target genes, we identified a chemokine CCL2. The lack of CCL2 suppressed the growth of tumor volume, and decreased macrophages and increased killer T cells in the tumor tissues, suggesting that LLC cells evade immune surveillance by increasing CCL2 expression via HuR.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

今回、がんによる免疫逃避機構の一つとしてHuRを介したCCL2発現誘導が存在することが示唆された。本研究は抗腫瘍免疫応答の分子機構の一つを明らかにしたという学術的意義にとどまらず、HuRやCCL2が新たな免疫チェックポイント阻害剤の標的となり得ることを示唆している点で大きな社会的意義もある。