| Project/Area Number |
18K08550
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Saitama Medical University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | neuroblastoma / 免疫チェックポイント阻害 / dendritic cell / tumor infiltrating cell / ADCP / 神経芽腫 / 腫瘍浸潤リンパ球 / 腫瘍浸潤樹状細胞 / 小児神経芽腫 / 腫瘍免疫 / 自然免疫 / 免疫チェックポイント遮断 / マウス神経芽腫モデル / 神経芽細胞腫 / 腫瘍免疫学 / 免疫療法 / chemoimmunotherapy / 免疫checkpoint遮断 |
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| Outline of Final Research Achievements |
The effect of immune checkpoint inhibitor on mouse neuroblastoma was investigated and host immune cells were analyzed in the tumor microenvironment. Neuro-2a cells were inoculated subcutaneously into mice, followed by intraperitoneal injection of antibodies targeting PD-1 and PD-L1. Tumor-infiltrating cells were analyzed. Growth of subcutaneous tumors was significantly suppressed, and PD-L1-expressing tumor cells were depleted by the antibody treatment. Neuro-2a cells opsonized by the anti-PD-L1 antibody were phagocytosed in the in vitro setting. In the treated tumor microenvironments, CD8+ lymphocyte and CD11c+ MHC II+ cells were accumulated. Immune suppressive effects of CD11b+Gr-1+ myeloid-derived suppressor cells by the administration of anti-PD-1 and PD-L1 antibodies were not observed. The possibility that co-administration of anti-PD-1 and anti-PD-L1 antibodies have a synergistic effect on inhibition of tumor growth and could be an effective therapy against neuroblastoma.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性進行小児神経芽腫に対する新たな免疫療法として、抗PD-1抗体PD-L1抗体の同時投与は抗腫瘍効果を示すことを確認し、pre clinical dataとして提供することができた。さらにこの抗体治療の効果のメカニズムには腫瘍に浸潤するリンパ球と貪食細胞が関与し、Antigen dependent cell phagocytosisの効果が有効に働いていることが示唆された。これらの結果は神経芽腫に対する新たな免疫治療の可能性を提示しながら、さらに腫瘍免疫学という基礎医学領域における新たな知見を示すことができた。これは腫瘍免疫学に関する発展に大きく貢献できる可能性があり意義が大きい。
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