Development of novel treatment to target immune suppressive cells in tumor microenvironment

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K16892
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Chiba University
• Principal Investigator: Ihara Fumie 千葉大学, 大学院医学研究院, 助教 (40779906)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: 制御性T細胞 / 頭頸部扁平上皮癌 / 骨髄性抑制細胞 / effector Treg / NKT細胞

Outline of Final Research Achievements

Regulatory T cells (Treg) reportedly play a crucial role in suppressing anti-tumor immunity in advanced cancer patients. We demonstrated increased numbers of activated Tregs in the peripheral blood of head and neck cancer (HNC) patients and confirmed that Tregs exerted a potent suppressive effect on other immune cells. Thus, we aimed to detect activated Treg-specific genes as a diagnostic biomarker for recurrence or metastasis of HNC and evaluate the utility of paclitaxel (PTX) in selectively suppressing the Treg function.
We identified several candidate genes whose expression was specific for Tregs derived from advanced HNC patients. Low-dose PTX suppressed Treg proliferation and the cytokine function, but not in cytotoxic T cells. The suppressive effects of PTX on Tregs could lead to the restoration of other immune cell functions, such as the cytotoxic activity of NKT cells. Our results suggest the possible utility of Treg-targeted therapy as a therapeutic strategy for advanced HNC.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌患者では、増加した活性型Tregにより臨床経過が不良となることから、パクリタキセルや、活性型Tregに特異的な遺伝子や表面抗原などを標的とした新規治療の開発は、Tregの抑制効果を減弱させ、担癌患者における免疫抑制の解除につながることから、今後の頭頸部癌患者の新たな治療戦略の確立という点において非常に有意義と考える。