Development of a novel liver cancer therapy by inducing chemotaxis of CD4-positive killer T cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17018
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: University of Fukui
• Principal Investigator: Naito Tatsushi 福井大学, 学術研究院医学系部門(附属病院部), 助教 (60529329)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CD4陽性キラーT細胞 / 肝癌 / ケモカイン / 多重染色 / 次世代シーケンサー

Outline of Final Research Achievements

This study aims to elucidate the dynamics of CD4+ killer T cells (CD4+CTL) with direct cytotoxic activity in hepatocellular carcinoma tumor tissue, a newly recognized class of CD4-positive cells that have been considered to have helper activity in immunity. During the study period, we established a mouse orthotopic hepatocellular carcinoma model using the mouse hepatoma cell line BNL 1ME A.7R.1 (BNL). Using TSA immunohistochemical staining, which allows simultaneous 7-color multiple staining, we analyzed the intratumoral localization and population of immune cells such as CD4+CTLs, CD8+CTLs, helper T cells, regulatory T cells, and macrophages. In addition, differences in T cell localization between background liver and hepatocellular carcinoma were identified.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

肝癌腫瘍組織において背景肝と腫瘍部で異なる免疫細胞が分布していることが明らかとなった。T細胞およびマクロファージにおいても、腫瘍の進展と制御において形態・役割の異なった細胞が存在し関与していることが示唆された。白血球を遊走させるケモカインを制御することで、癌部にCD4+CTLを誘導するという新たな治療戦略が考えられる。本研究成果は、再発を繰り返す予後不良な癌腫である肝細胞癌において新規の抗癌治療法の確立に寄与するという社会的意義がある。