| Project/Area Number |
17K07207
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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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| Research Field |
Tumor diagnostics
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| Research Institution | Japanese Foundation for Cancer Research (2020)
National Cancer Center Japan (2017-2019) |
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Principal Investigator |
YAMASHITA Makiko 公益財団法人がん研究会, 有明病院 がん免疫治療開発部, 研究員 (00380668)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 腫瘍免疫 / 免疫モニタリング / 抗腫瘍免疫 / 抗体医薬 / 薬効評価・予測 / 有害事象 |
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| Outline of Final Research Achievements |
In this study, we constructed a panel that can analyze the quantity and properties of various lineage cells, T cells, and myeloid cells using a multicolor flow cytometer that can stain up to 18 colors simultaneously. As a result of analysis and comparison of lymphocyte populations in peripheral blood of healthy subjects and patients with solid tumors using the panel, it was confirmed that the expression of various checkpoint molecules on T cells was up-regulated in cancer patients compared to healthy subjects, which is consistent with previous reports. On the other hand, in myeloid cells, the expression of PD-L1 was upregulated in cancer patients, but there were no significant differences in the expression of other molecules. These results suggest that the PD-1/PD-L1 pathway plays an important role in anti-tumor immunity, as T cells in circulating lymphocytes are exhausted in cancer patients, and PD-L1 expression in myeloid cells tends to be higher in cancer patients.
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| Academic Significance and Societal Importance of the Research Achievements |
担がん生体における免疫応答は、マウスモデルでは非常に詳細な解析がなされているものの、実際の実地臨床においては、がん患者自身の免疫機能の実態についてほとんど知られることがないまま治療が行われている。ヒトにおける薬剤投与後の免疫応答性はマウスでは再現できないことは広く知られており、よって患者由来検体の解析を通じてヒト生体内での疾患病態を直接的に検討することは非常に重要である。本研究により、患者の免疫病態をモニタリングするための基盤整備が進めば、そのエフェクター機能やそれを制御する各種免疫細胞のポピュレーションの変化を、実際に薬剤が投与される患者において経時的にモニタリングすることが可能となる。
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