Role of the Rac activator DOCK1 in immune evasion by tumor

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02406
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kyushu University
• Principal Investigator: Uruno Takehito 九州大学, 生体防御医学研究所, 准教授 (80532093)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 腫瘍制御 / 細胞骨格 / シグナル伝達 / 低分子量Gタンパク質 / 免疫回避

Outline of Final Research Achievements

The role of DOCK1 and its related proteins in tumor immune evasion was investigated. DOCK1-Rac signal was associated with the expression of some of the interferon-responsive genes as well as STAT3 phosphorylation. Genetic ablation of DOCK1 in cancer cells resulted in marked infiltration of immune cells into tumor in vivo. A lipid metabolite that functions as an endogenous inhibitor of DOCK2 and regulates immune cell motility was identified. Thus, the study elucidates the critical roles of DOCK1 and related proteins in tumor-immune interactions, which could be exploited for the future development of novel anticancer therapeutics.

Free Research Field

機能生化学

Academic Significance and Societal Importance of the Research Achievements

がんの悪性化において、がん細胞が周囲の免疫細胞の攻撃から逃れるメカニズム（免疫回避）の重要性が明らかとなっている。しかしながら、腫瘍-免疫細胞相互作用の実体には不明な点が多い。本研究課題は、DOCK1及び関連分子を介した免疫回避の仕組みの一端を明らかにし、既知の免疫抑制機構とは異なる新たな免疫回避機構の存在を示すことが出来た。その成果は将来的には腫瘍免疫をターゲットにした新たな治療戦略の開発や診断マーカーの創出につながることが期待される。