| Project/Area Number |
18K14578
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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 42020:Veterinary medical science-related
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| Research Institution | Obihiro University of Agriculture and Veterinary Medicine |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 免疫チェックポイント / PD-1 / PD-L1 / CTLA-4 / リンパ腫 / 犬 / 免疫療法 / 腫瘍免疫 |
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| Outline of Final Research Achievements |
Flow cytometric analysis revealed that the expression of PD-1 on CD4+ peripheral and tumor infiltrating lymphocytes and CTLA-4 on CD4+ peripheral lymphocytes was significantly higher in the B cell lymphoma group than in the control group. Dogs with CTLA-4 levels below the cutoff values on peripheral CD4+, CD8+, and tumor infiltrating CD4+ lymphocytes had significantly longer survival than dogs with values above the cutoff.
Lymphoma cells and peripheral lymphocytes which were obtained from lymphoma case were co-cultured under PD-L1 antibodies. As a results, the increased PBMC and IL-10 production were observed. In addition, the increased IFN-γ production was observed in PD-L1 overexpression case.
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| Academic Significance and Societal Importance of the Research Achievements |
犬B細胞性リンパ腫においても免疫チェックポイント分子、とくにPD-1およびCTLA-4の発現増加が示唆され、予後との関連性が見い出された。また抗体添加により細胞増殖が促され、PD-L1高発現症例ではIFN-γの産生亢進もみられた。獣医学領域において宿主免疫側の免疫チェックポイント発現はほとんど検討されておらず、本研究結果は免疫チェックポイント阻害療法の犬リンパ腫への適応を正当化する根拠になりえるものと思われた。
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