Elucidation and Control of Pancreatic Cancer Immune Evasion Mechanisms through Single-Cell Analysis of CAF-Cell Interactions.
| Project/Area Number |
21K16424
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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 55020:Digestive surgery-related
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| Research Institution | Saga University (2022)
Kyushu University (2021) |
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Principal Investigator |
Takesue Shin 佐賀大学, 医学部, 助教 (30883425)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 膵癌 / シングルセル発現解析 / 癌微小環境 / 癌関連線維芽細胞 / 腫瘍免疫 / 膵癌関連線維芽細胞 / 新規治療標的 / 膵癌微小環境 / 単一細胞解析 / 免疫逃避機構 / CAF / 免疫治療薬 |
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| Outline of Research at the Start |
本研究では、膵癌自然発癌モデルマウス由来の膵癌細胞をC57BL/6マウスに同所移植することで腫瘍免疫を含めた膵癌微小環境再現モデルを作成し、腫瘍形成初期から進行期まで多段階的に単一細胞解析することで、膵癌細胞がいかにして免疫逃避機構を確立し進展するかを明らかにする。また、癌の浸潤において重要といわれているcancer associated fibroblast(CAF)の働きに着目し、癌細胞や免疫細胞などの他の細胞種との間の相互作用という観点から膵癌の免疫逃避機構構築の機序を明らかにし、関連する細胞種および因子の制御を可能にすることで新たな免疫治療薬の開発につなげる。
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| Outline of Final Research Achievements |
The aim of this study was to elucidate the changes in the tumor microenvironment during the early stages of pancreatic cancer formation and progression, using single-cell expression analysis of tumor tissue. The study aimed to identify novel cell populations involved in the immune evasion mechanisms of pancreatic cancer cells and establish novel therapeutic strategies to control them.
A mouse model was created by transplanting pancreatic cancer cells derived from spontaneously developed pancreatic cancer in mice, and the impact on the tumor microenvironment by cancer-associated fibroblasts (CAFs) was explored. Co-transplantation with CAFs promoted tumor formation and revealed a reduced infiltration of CD8-positive T cells. Furthermore, morphological classification of organoids derived from surgical specimens of pancreatic cancer revealed a higher dependency on cancer microenvironmental factors secreted by CAFs in well-differentiated pancreatic cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では膵癌の進展において癌間質中の癌関連線維芽細胞（CAF）が腫瘍抑制的に作用するCD8陽性リンパ球の誘導を抑制することにより膵癌の進展を促進する可能性が示された。
膵癌は極めて予後不良な癌種であり、薬物治療の進歩にも関わらず治療効果は限定的である。本研究の成果により癌関連線維芽細胞を免疫細胞の相互作用が新たな治療標的になる可能性が示唆され、膵癌の薬物治療の進歩を通して社会に貢献できると考えられる。
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Report
(3 results)
Research Products
(4 results)
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[Journal Article] Neoadjuvant chemotherapy enhances anti-tumor immune response of tumor microenvironment in human esophageal squamous cell carcinoma2023
Author(s)
Sho Okuda, Kenoki Ohuchida, Shoichi Nakamura, Chikanori Tsutsumi, Kyoko Hisano, Yuki Mochida, Jun Kawata, Yoshiki Ohtsubo, Tomohiko Shinkawa, Chika Iwamoto, Nobuhiro Torata, Yusuke Mizuuchi, Koji Shindo, Taiki Moriyama, Kohei Nakata, Takehiro Torisu, Takashi Morisaki, Takanari Kitazono, Yoshinao Oda, Masafumi Nakamura.
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Journal Title
iScience
Volume: 26
Pages: 106480-106480
Related Report
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