Search for new therapeutic strategies targeting regulatory T cells for lung cancer with pulmonary fibrosis
| Project/Area Number |
17K09663
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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 |
Respiratory organ internal medicine
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| Research Institution | Nara Medical University |
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Principal Investigator |
Shigeto Hontsu 奈良県立医科大学, 医学部, 講師 (90458034)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 利洋 奈良県立医科大学, 医学部, 教授 (00595712)
北畠 正大 奈良県立医科大学, 医学部, 講師 (60457588)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 制御性T細胞 / 肺線維症合併肺癌 / 肺線維症 / 肺癌 / 特発性間質性肺炎合併肺癌 / 特発性肺線維症 / 合併肺癌 / 制御性Ｔ細胞 |
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| Outline of Final Research Achievements |
Lung cancer patients with idiopathic pulmonary fibrosis (IPF) who underwent surgical treatment for 5 years from January 2012 at Nara Medical University hospital were enrolled as a test group, and patients adjusted for age, stage, histology, etc. were enrolled as control group for progression-free survival (PFS), overall survival (OS), tumor-infiltrating regulatory T cells (Treg) and cytotoxic T cells (CTL) were investigated. Lung cancer patients with IPF was significantly worse in both PFS and OS, and was associated with an increase in the number of tumor infiltrating Tregs and a decrease in the tumor infiltrating CTL / Treg ratio as prognostic factors. A lung cancer cell line (LLC) was inoculated into a bleomycin-induced lung fibrosis mouse model to create a lung cancer model with IPF. In the lung cancer model with IPF, tumors increased and expanded significantly, suggesting that Treg infiltration into tumors is associated with lung fibrosis and tumor enlargement.
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| Academic Significance and Societal Importance of the Research Achievements |
肺線維症合併肺癌患者の予後不良因子の免疫学的機序の1つとして、制御性T細胞（Treg）の腫瘍浸潤の増加および細胞傷害性T細胞/Treg比が低下する事が明らになった。更に、肺線維症合併肺癌マウスモデルにおいて、腫瘍増大および肺線維化の双方にTregの関与が示唆された。肺線維症合併肺癌の治療において腫瘍増大および肺線維化の両方を抑制する治療ターゲットとしてTregの重要性を示唆する知見が得られた。今後、抗体によるTregの除去やTregの分化、活性化および増殖に関与する遺伝子や分子を標的とした治療の開発により、肺線維症合併肺癌の治療成績の向上につながると考えられる。
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Report
(5 results)
Research Products
(13 results)
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[Presentation] The safety assessment of crizotinib and alectinib from real world date of 840 ALK-inhibitor naive patients with NSCLC harboring ALK-rearrangement (WJOG9516L)2019
Author(s)
K. Kunimasa, K. Ito, T. Yamanaka, D. Fujimoto, M. Mori, K. Maeno, K. Tomomatsu, A. Tamura, H. Tanaka, S. Watanabe, S. Teraoka, O. Hataji, K. Suzuki, S. Hontsu, S. Hara15, A. Bessho, A. Kubo, M. Okuno, K. Nakagawa, N. Yamamoto
Organizer
ESMO 2019 Congress
Related Report
Int'l Joint Research
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