| Project/Area Number |
18K16093
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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 54010:Hematology and medical oncology-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
Noyori Osamu 熊本大学, ヒトレトロウイルス学共同研究センター, 特定事業研究員 (30737151)
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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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | DLBCL / IL-34 / M-CSF / マクロファージ / Interleukin-34 / M-CSF receptor / IL-34の異所性発現 / バーキットリンパ腫由来細胞のオートクライン増殖 / non-GCBタイプ細胞株によるIL-34の供給 / Fms |
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| Outline of Final Research Achievements |
Infiltration of macrophages through the tyrosine kinase receptor CSF1R is a poor prognosis factor in various solid tumors. However, the significance of CSF1R ligands, particularly, the newly discovered IL-34 in haematological malignancies, is not fully understood. We therefore analysed the role of IL-34 in diffuse large B-cell lymphoma (DLBCL), the most common subtype of malignant lymphoma.
Several lymphoma tissues showed a clear IL-34 signal, and such signal was detectable in 36% of patients. DLBCL cell lines also expressed IL-34. Interestingly, the percentage of IL-34+ patients in the activated B-cell subtype was significantly higher than that in the germinal centre B-cell subtype. More interestingly, IL-34+ patients showed shorter survival periods and higher number of macrophages in lymphoma tissues. The recruitment of monocytes is likely the first step for the higher macrophage density in the IL-34+ lymphoma tissues. Indeed, IL-34 induced the migration of monocytic cells.
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| Academic Significance and Societal Importance of the Research Achievements |
M-CSFおよびIL-34は腫瘍組織における免疫抑制性の腫瘍関連マクロファージの増加を促し、様々な固形腫瘍の増悪に寄与するという負の側面を有することが知られている。
本研究では、これらサイトカインは固形腫瘍と類似したメカニズムで血液系腫瘍の増悪にも寄与していることを初めて示した。本課題により、これらサイトカインに共通のレセプターFmsに対する阻害剤が、広範囲の腫瘍に応用できる可能性を示唆する重要な知見が得られた。
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