Association between anti-tumor effect of Kampo combined with anti-PD-1 antibody and interstinal microbiota
Project/Area Number |
20K18128
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56030:Urology-related
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Research Institution | Kurume University |
Principal Investigator |
Ueda Kosuke 久留米大学, 医学部, 講師 (60569440)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 腎細胞癌 / 腸内細菌 / 免疫チェックポイント阻害剤 / 腸内細菌叢 / 漢方薬 / 免疫チェックポイント阻害薬 / 抗PD-1抗体 |
Outline of Research at the Start |
免疫チェックポイント阻害剤の効果予測因子として、腸内細菌叢が注目されている。近年、菌種の多様性が治療効果に影響を及ぼす可能性や、抗生剤投与が治療効果の減弱に関連している可能性が報告されている。さらに、漢方薬に含まれる様々な成分のprebioticsとしての働きが腸内細菌叢を変化させ、生体遺伝子の変化が起こり、免疫機能を変化させることが示されている。今回の研究では、免疫チェックポイント阻害剤と漢方薬との併用効果を確認することにより、将来的に効果的な免疫チェックポイント阻害剤の治療戦略を探索する。
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Outline of Final Research Achievements |
In this study, we evaluated the effects of Japanese traditional herbal medicines which called as Kampo on the intestinal microbiota in renal cell carcinoma (RCC) and the antitumor effect of its combination with anti-PD-1 antibody. Regarding the effect of Kampo on tumor growth inhibition, it was shown that tumor growth was most inhibited in mice transplanted with RCC cell lines that were treated with Daiokanzoto, and that the administration of Kampo increases the diversity of the intestinal microbiota. In the study of the combination of Kampo and anti-PD-1 antibody, most effective anti-tumor effect was observed in the group that treated with Daikenchuto and anti-PD-1 antibody. However, no significant change was observed in the intestinal microbiota compared to the other groups. Although the combination of Kampo and anti-PD-1 antibodies may enhance the anti-tumor effect against RCC, the association with the intestinal microbiota was not clarified.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では腎細胞癌における漢方薬が与える腸内細菌叢への影響、漢方薬と免疫チェックポイント阻害剤である抗PD-1抗体との併用による治療効果を評価した。腫瘍増殖に与える影響に関する検討では、漢方薬の投与により抗腫瘍効果や腸内細菌叢の変化に影響は認められるものの薬剤間において顕著な変化は認められなかった。漢方薬と抗PD-1抗体を用いた検討においても大黄甘草湯と抗PD-1抗体を併用した群において高い抗腫瘍効果が認められたが、腸内細菌叢には有意な変化は確認されなかった。漢方薬と抗PD-1抗体の併用により腎細胞癌に対する抗腫瘍効果を高める可能性はあるが、腸内細菌叢との関連については明らかとならなかった。
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Report
(4 results)
Research Products
(15 results)
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[Journal Article] Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma2020
Author(s)
Osawa Takahiro,Kojima Takahiro,Hara Tomohiko,Sugimoto Mikio,Eto Masatoshi,Takeuchi Ario,Minami Keita,Nakai Yasutomo,Ueda Kosuke,Ozawa Michinobu,Uemura Motohide,Miyauchi Yasuyuki,Ohba Kojiro,Suzuki Toshiro,Anai Satoshi,Shindo Tetsuya,Kusakabe Naohisa,Tamura Keita,Komiyama Motokiyo,Goto Takayuki,Yokomizo Akira
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Journal Title
Cancer Science
Volume: 111
Issue: 7
Pages: 2460-2471
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Efficacy and safety of second-line axitinib in octogenarians with metastatic renal cell carcinoma2020
Author(s)
Nakai Yasutomo,Takeuchi Ario,Osawa Takahiro,Kojima Takahiro,Hara Tomohiko,Sugimoto Mikio,Eto Masatoshi,Minami Keita,Ueda Kosuke,Ozawa Michinobu,Uemura Motohide,Miyauchi Yasuyuki,Ohba Kojiro,Kashiwagi Akira,Murakami Masaya,Sazuka Tomokazu,Yasumoto Hiroaki,Morizane Shuichi,Kawasaki Yoshihide,Morooka Daichi,Shimazui Toru
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Journal Title
Journal of Geriatric Oncology
Volume: 30
Issue: 5
Pages: 30534-30538
DOI
Related Report
Peer Reviewed
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[Presentation] Association between soluble immune checkpoint molecules expression and efficacy of IO combination therapy in advanced renal cell carcinoma2023
Author(s)
Ueda Kosuke, Uemura Keiichiro, Suekane Shigetaka, Ito Naoki, Ogasawara Naoyuki, Kurose Hirofumi, Hiroshge Tasuku, Chikui Katsuaki, Nishihara Kiyoaki, Nakiri Makoto, Matsuo Mitsunori, Igawa Tsukasa
Organizer
第110回 日本泌尿器科学会総会
Related Report
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