| Project/Area Number |
17K15037
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Sakai Chika 国立研究開発法人国立がん研究センター, 先端医療開発センター, 研究員 (90622845)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ミトコンドリア / がん微小環境 / 制御性T細胞 / がん免疫療法 / 代謝 |
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| Outline of Final Research Achievements |
Tumor cells primarily use glucose for glycolytic energy production and release lactate, creating a low-glucose and high-lactate environments. Despite this severe environment, it was reported that a large number of CD25+CD4+Tregs are present in tumors and additionally they are activated (effecter Tregs; eTregs). Because of their roles in promoting tumor immune escape and progression, increased numbers of eTregs in tumors have been associated with poor survival in many solid tumors.
In this study, we revealed eTregs have a survival advantage among other lymphocytes in tumor site by using lactate for energy metabolism. The lactate metabolism by eTregs should be a promising target for the novel cancer immunotherapy.
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| Academic Significance and Societal Importance of the Research Achievements |
がん免疫療法は患者の免疫応答を強化し、がん細胞を攻撃・排除する。しかし全身の免疫応答を過度に強化してしまうと自己免疫疾患等の副作用がある他、臨床試験で十分効果が認められない治療法も多い。奏功率が比較的高い免疫チェックポイント阻害剤の併用療法でも50％程度との報告がある。そこで現在、より効果的で副作用の少ない新規の免疫療法の開発が求められている。
本研究は、従来とは異なる作用機序で、かつ腫瘍局所に限局して作用する免疫療法の標的を見出すことに成功した。本研究を元に腫瘍局所において抗腫瘍免疫の妨げとなるTregの機能抑制が実現可能であると考えられる。
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