2018 Fiscal Year Final Research Report
Development of prediction of responder in cancer immunotherapy by using radiation
| Project/Area Number |
16K07173
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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 |
Tumor therapeutics
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| Research Institution | Osaka University |
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Principal Investigator |
Takahashi Yutaka 大阪大学, 医学系研究科, 特任講師(常勤) (40353461)
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| Co-Investigator(Kenkyū-buntansha) |
玉利 慶介 大阪大学, 医学系研究科, 特任助教(常勤) (30718995)
小川 和彦 大阪大学, 医学系研究科, 教授 (40253984)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | 放射線 / 重粒子線 / 腫瘍免疫 / アブスコパル効果 |
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| Outline of Final Research Achievements |
Immune checkpoint inhibitor has been playing an important role in controlling metastatic tumors. However, only limited patients experience durable response. Therefore development of strategy to increase the responder and exploring biomarker to predict the responder is an urgent issue. The purpose of this study was to investigate whether use of various radiation including X-ray and particle beam combined with dual immune checkpoint blockade (Anti-PD-L1 and anti-CTLA-4 antibodies: P1C4) contribute to the control of tumors out-side radiation field, and addition of radiation to immune checkpoint blockade alters immune micro environment. We found that both X-ray and carbon ion irradiation enhanced the efficacy of P1C4 both for irradiated tumors and tumors out-of-radiation field with the increase of CD8 to Treg ratio. Although further study is necessary, tumor microenvironment analysis after radiation therapy might be useful to predict responder for immune checkpoint blockade therapy.
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| Free Research Field |
Radiation biology
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| Academic Significance and Societal Importance of the Research Achievements |
免疫チェックポイント阻害剤は遠隔転移を有する症例に対しても効果が得られているが、奏効率は依然と低く、高奏効率化と予測法の開発が求められている。私たちは、まず、X線、または重粒子線と免疫チェックポイント阻害剤を併用することで、奏効率の向上が得られるかどうかを骨肉腫マウスモデルを用い、骨肉腫細胞を両脚に移植し、片方のみに照射する系で研究した。その結果、放射線と抗PD-L1抗体と抗CTLA-4抗体を併用することで、照射腫瘍のみならず、照射野外の腫瘍に対しても高率に抗腫瘍効果が得られ、有意に生存が延長し、腫瘍免疫環境も変化していた。本研究は放射線と免疫療法の併用の臨床利用の合理性を与えるものである。
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