2022 Fiscal Year Final Research Report
Generation of novel cancer immune therapy by regulation of IL-17 producing gd T cells
Project/Area Number |
21K19518
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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Research Institution | Gunma University |
Principal Investigator |
Shirabe Ken 群馬大学, 大学院医学系研究科, 教授 (70264025)
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Co-Investigator(Kenkyū-buntansha) |
矢島 俊樹 群馬大学, 大学院医学系研究科, 准教授 (20346852)
塚越 真梨子 群馬大学, 大学院医学系研究科, 助教 (60781317)
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Project Period (FY) |
2021-07-09 – 2023-03-31
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Keywords | IL-17産生γδ型T細胞 / Vγ6陽性γδ型T細胞 / 転移性肺腫瘍 |
Outline of Final Research Achievements |
To deplete the either γδ T cells or IL-17-producing γδ T cells, C57BL/6 mice were treated with either anti-γδ mAb or anti-Vγ6 mAb before tumor inoculation, and then intravenously administrated with B16F10 or 3LL. Metastatic lung nodules were examined on day 14 after tumor inoculation. The numbers of metastatic lung nodule in γδ T cell-depleted mice or IL-17-producing γδ T cell-depleted mice were decreased on day 14 compared with those in control IgG-treated mice. We assessed the CD8, CD4 or Foxp+ T cells of peripheral lung tumors in those mice and found that the numbers of CD8+ T cells, but not both CD4+ T cells and Foxp+ T cells, were significantly increased in both γδ T cell-depleted mice and IL-17-producing γδ T cell-depleted mice compared with those in control IgG-treated mice. IL-17-producing γδ T cells may play critical role in the negative regulation of activated CD8+ T cells during the generation of lung metastasis.
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Free Research Field |
Cancer immune therapy
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Academic Significance and Societal Importance of the Research Achievements |
これまで腫瘍免疫応答においてγδ型T細胞は免疫を活性化する役割と抑制する役割が報告され不明な点が多かった。本研究成果からIL-17産生γδ型T細胞(Vγ6陽性)は肺転移において免疫を抑制する役割を担っていることが明らかとなった。そのメカニズムとして腫瘍免疫応答で中心的な役割を担う活性化CD8T細胞を抑制している可能性が示唆された。 今後、我々が確立した抗原特異的CD8T細胞を詳細に解析できるモデルを用いて、その抑制メカニズムを詳細に解析することより、γδ型T細胞を制御する新規癌免疫療法の開発につながる点で意義の高い研究となる。
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