| Project/Area Number |
24390306
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Hyogo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
笹子 三津留 兵庫医科大学, 医学部, 教授 (40143490)
菊池 正二郎 兵庫医科大学, 医学部, 准教授 (70381960)
前山 義博 兵庫医科大学, 医学部, 非常勤講師 (80614031)
田中 義正 長崎大学, 医歯(薬)学総合研究科, 准教授 (90280700)
久保 秀司 兵庫医科大学, 医学部, 准教授 (10441320)
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| Research Collaborator |
LI Wen
MA Zhifeng
Yosif El-Darawish
SEKI Hatsuka
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| Project Period (FY) |
2012-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
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| Keywords | IL-18 / 免疫チェックポイント阻害薬 / 抗CTLA4抗体 / 抗PD-L1抗体 / NK細胞 / Treg / CD8陽性T細胞 / 抗CTLA4 抗体 / 抗PD-１抗体 / 抗PD-L１抗体 / IDO阻害剤 / ミトコンドリア / オートファジー / がん免疫治療 / CTLA4 / PD-L1 / CD８陽性T細胞 / CD8陽性細胞 / γδT細胞 / 抗腫瘍効果 / ヘルパーNK細胞 / γδＴ細胞 / γδTリンパ球 / サイトカイン / 胃がん / 腹膜播種 / 微小環境 |
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| Outline of Final Research Achievements |
This study was carried out on the trial to examine the utility of interleukin-18 (IL-18) for cancer immunotherapy. Recent development of immune checkpoint inhibitors targeting PD-1 or PD-L1 for cancer immunotherapy have made a breakthrough and opened new era in cancer therapy. This therapy requires further progress in augmentation of efficacy and suppression of adverse events. Using an animal model of cancer peritoneal dissemination, we demonstrated that IL-18 markedly augments the efficacy of immune checkpoint inhibitors suppressing tumor growth and prolonging survival of mice inoculated with tumor cells. As a mechanism, it was considered that IL-18 strongly enhances expansion of effector cells including NK cells, γδ T cells, and CD8+ T cells, and oppositely suppresses Treg cells. These results demonstrated utility of IL-18 in cancer immunotherapy and suggested usage of IL-18 for wider range of immunotherapy.
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