2024 Fiscal Year Final Research Report
The Pancreatic Cancer Mini-Ecosystem: Roles of the Microbiome and Tumor-Associated Neutrophils
| Project/Area Number |
23K24183
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| Project/Area Number (Other) |
22H02922 (2022-2023)
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Multi-year Fund (2024)
Single-year Grants (2022-2023) |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐田 政史 九州大学, 医学研究院, 共同研究員 (10783508)
水内 祐介 九州大学, 大学病院, 助教 (20849088)
永吉 絹子 九州大学, 大学病院, 助教 (90761015)
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| Project Period (FY) |
2024-04-01 – 2025-03-31
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| Keywords | 腫瘍関連好中球 / TAN / マイクロバイオーム / Fusobacterium nucleatum / CXCL1 / CXCR2 / Nectin2 |
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| Outline of Final Research Achievements |
This study revealed that the microbiome and tumor-infiltrating neutrophils play key roles in shaping the immunosuppressive microenvironment of pancreatic cancer.
"Fusobacterium nucleatum" induced CXCL1 in cancer cells, activating the CXCR2 pathway to recruit neutrophils and myeloid-derived suppressor cells, which suppressed CD8+ T cell function. In addition, tumor associated neutrophils highly expressed Nectin2, contributing to T cell exhaustion. Inhibiting Nectin2 or ER stress reduced tumor progression, suggesting new therapeutic strategies targeting neutrophils and the microbiome in pancreatic cancer.
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| Free Research Field |
医歯薬学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、膵がんの進展を支える免疫抑制性微小環境の形成において、腫瘍関連好中球およびマイクロバイオームが果たす中心的な役割を明らかにした点で、極めて学術的意義が高い。特に、"Fusobacterium nucleatum"によるCXCL1-CXCR2経路の活性化や腫瘍関連好中球の免疫抑制分子Nectin2が、CD8+T細胞の抑制と腫瘍の悪性化に寄与していることを示した。本知見は、これら分子経路を標的とした免疫療法開発の新たな基盤となるものであり、膵がんの治療選択肢を広げる社会的意義も大きい。
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