| Project/Area Number |
16K10618
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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 |
Digestive surgery
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| Research Institution | Osaka University (2017-2018)
Department of Clinical Research, National Hospital Organization Kure Medical Center (2016) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三善 英知 大阪大学, 医学系研究科, 教授 (20322183)
江口 英利 大阪大学, 医学系研究科, 准教授 (90542118)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 膵癌 / 微小循環癌細胞 / 腹腔内遊離癌細胞 / テロメスキャン / バイオマーカー / 糖鎖 / 糖鎖医薬 / 創薬 / オリゴデンドリマー |
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| Outline of Final Research Achievements |
We tested novel methods for viable CTCs (v-CTC) isolation in pancreatic cancer (PC) as “liquid biopsy”. We analyzed the PD-L1(L1) expression in both PC tumors and v-CTCs. To detect v-CTCs, we employed a telomerase-specific replication-selective adenovirous expressing GFP.To assess L1 expression in PC tissues (IHC) and v-CTCs, L1 IHC kit and anti-human L1 mAb were employed.
S group: 24 pts were enrolled. No v-CTCs were detected in 6 pts at both before and after resection, and 5 of 6 pts survived without recurrence. N group: 15 PC pts were enrolled. No v-CTCs were detected in 5 pts, and 5 pts survived without recurrence. Marked increase in CTC counts was observed after NACRT in 5 of 6 CTC-positive pts before NACRT, and 3 of 5 pts developed liver metastasis and died. PD-L1 expression:89% of detectable v-CTCs were positive for L1-expression.
In conclusion, viable CTC detection appears as a promising prognostic marker. Immunotherapy with anti-PD-1/PD-L1 Abs may target v-CTCs.
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| Academic Significance and Societal Importance of the Research Achievements |
v-CTC検出の有無から見た切除可能膵癌に対する治療方針として、術前v-CTC陰性例ではNACRTまたはNACを先行し根治切除を行い術後補助療法を追加する。
一方、術前v-CTC検出陽性例では、術前化学療法を行い、その後根治切除を実施する治療選択が予後改善につながる可能性が示唆された。
膵癌患者の末梢血中で検出されたv-CTC上にはPD-L1発現を高率（約90％）に確認でき、切除膵癌の原発腫瘍巣でのPD-L1発現率 (<1% [negative]:9例, 10%:6例, 20%:4例, 40%:2例)と大きな差を認めた。膵癌根治をめざす治療戦略として免疫チエックポイント阻害剤の有効性が期待できる。
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