| Project/Area Number |
18K16652
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 骨肉腫 / 抗PD-1抗体 / Wnt / PD-1 / 免疫細胞 |
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| Outline of Final Research Achievements |
In this research, we evaluated the efficacy of anti-PD-1 antibody for osteosarcoma and the dynamics of immune cells in tumor microenvironment. According to the results, the long-term administration of anti-PD-1 antibody suppressed the increase of tumor volume and improve the overall survival in the osteosarcoma heterotopic transplantation model mouse. Also, the regulatory T cells (Treg) especially the activated Treg(Ki67+) decreased by the administration of anti-PD-1 antibody.
On the other hand, Wnt3a, Lrp5 and Wnt5a positive are correlated in the clinical specimen of osteosarcoma.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究結果は、抗PD-1抗体が骨肉腫の腫瘍体積の増加を抑制し、全生存率を改善することを示した。また、抗PD-1抗体投与により腫瘍内のTregが減少することが分かり、抗PD-1抗体の抗腫瘍効果における新しいメカニズムを示唆している。これらの研究成果は骨肉腫の治療における抗PD-1抗体を考えるうえで重要な基礎データとなる。また、臨床検体を用いた検討の結果は骨肉腫においてWnt古典経路及び非古典経路が協調的に働いている可能性を示しており、病態の理解やそれに伴う新規治療法の確立において有用な結果である。
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