| Project/Area Number |
18H02834
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
錦井 秀和 筑波大学, 医学医療系, 准教授 (30512834)
千葉 滋 筑波大学, 医学医療系, 教授 (60212049)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | がん微小環境 / T細胞リンパ腫 / TET2 / RHOA / Ｔ細胞リンパ腫 / 炎症細胞 / 微小環境 |
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| Outline of Final Research Achievements |
T-cell lymphoma is a subtype of hematological malignancies. The tumor tissues are markedly infiltrated with a variety of inflammatory cells. These inflammatory cells have been supposed to act as microenvironmental cells that support growth and survival of tumor cells. However, the specific mechanism has not been clarified at all. The principal investigator conducted a genome analysis of T-cell lymphomas, and found that T-cell lymphomas are sometimes derived from premalignant cells with loss-of-function mutations in Tet2 gene that encodes an epigenome-modifying enzyme. Furthermore, tumor cells also have acquired the G17V RHOA mutation (Nat Genet 2014). In this study, we elucidated the variety of inflammatory cells using single cell RNA sequencing and the relationship between gene mutations and expression.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、クローン造血に代表されるAITLという疾患について、炎症細胞プロファイルを明らかにする研究である。固形がん患者においても、クローン造血の頻度は25%と報告されており（Coombs, Cell Stem Cell 2018）、クローン造血のあるがん患者では、AITLと同様に、体細胞変異のある炎症細胞ががん細胞に浸潤し、微小環境細胞として働いている可能性がある。AITLにおける炎症細胞の異常プロファイルに関する研究成果は、がん微小環境の理解およびこれを標的とする治療に広く応用可能であると期待される。
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