| Project/Area Number |
17K16046
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokushima |
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Principal Investigator |
OGINO Hirokazu 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (20745294)
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| Research Collaborator |
AFROJ tania
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 線維細胞 / 免疫療法 / 分子細胞呼吸器学 / がん免疫療法 |
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| Outline of Final Research Achievements |
In this study, we investigated the immuno-modulatory function of fibrocytes in tumor immunity. First, we evaluated the expressions of several immune-checkpoint molecules on fibrocytes, and found that fibrocytes overexpressed not only PD-L1 but also CD54 and CD86. Fibrocytes significantly upregulated T-cells proliferation in the co-culture experiment,and these effects were cancelled by the blocking of CD54 or CD86.
The naive CD8+ T-cells did not express PD-1, however, the expression of PD-1 on T-cells was induced by the stimulation of IL-2. Fibrocytes significantly suppressed the T-cells proliferation under the stimulation of IL-2, however, these effects were cancelled by the blocking of PD-L1.
These results show that fibrocytes may activate naive CD8+ T-cells via co-stimulatory factors, such as CD54 or CD86, whereas that suppress the activated CD8+ T-cells via PD-L1.
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| Academic Significance and Societal Importance of the Research Achievements |
胸部悪性腫瘍領域においても免疫チェックポイント阻害薬（ICI）が盛んに用いられているが、一部の症例では本薬剤による治療効果が得られず、より良い治療戦略の構築および薬効を規定するバイオマーカーの開発が臨床上急務である。近年化学療法剤や血管新生阻害剤とICIの併用効果が報告されているが、至適併用法は未解明な部分が多い。
本研究では腫瘍間質に存在する線維細胞の腫瘍免疫における役割を解析し、上述の様に本細胞が腫瘍免疫を活性化する可能性が示唆された。本細胞を標的とする治療法の開発が癌免疫療法の有用性を向上させることにつながる可能性を含んでおり、本研究成果は学術的・社会的意義の大きいものであると考える。
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