Establishment and pathological analysis of novel immunotherapy by control of tryptophan-metabolizing enzymes in metastatic tumors
| Project/Area Number |
17K15785
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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 |
Laboratory medicine
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| Research Institution | Fujita Health University |
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Principal Investigator |
Hoshi Masato 藤田医科大学, 保健学研究科, 講師 (40633996)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | トリプトファン代謝 / KMO / IDO / KAT / キヌレニン / キサンツレン酸 / がん微小環境 / B16F10細胞 / B16F１０細胞 / IDO1 / IDO2 / 3-hydroxykynurenine / Ro61-8048 / ＩＤＯ１ / ＩＤＯ２ / Ｂ１６Ｆ１０ / ＫＭＯ / トリプトファン代謝産物 |
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| Outline of Final Research Achievements |
A mouse lung metastasis model was generated and the roles of tryptophan metabolism were analyzed. Kynurenine 3-monooxygenase gene deficient (KMOKO) mice, a rate-limiting enzyme for kynurenine metabolism, significantly inhibited tumor growth compared to wild-type mice. Similarly, tumor growth was inhibited in KMO inhibitor-treated mice. These results were also confirmed in a various tumor model.Interestingly, the tumor suppressive effect in KMOKO was abolished by administration of the 3-hydroxykynurenine and xanthurenic acid. Thus, we showed that a type of tryptophan metabolite was deeply involved in tumor growth.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、抗PD-1抗体などの免疫チェックポイント阻害剤の投与は、従来の治療と比較して飛躍的に治療効果を向上させた。一方で、未だ７割程度の患者では十分な効果が得られていなことや高額な医療費が問題点として上げられる。本研究では、上記問題点を解決するために、トリプトファン代謝に着目し、研究したところ、代謝酵素の一つであるKMOを阻害することで腫瘍細胞の増殖が、抑制できることを明らかにした。これらの成果は、現在の治療法で効果のない患者の新規治療法を考える上で、重要な知見であると考えられる。
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] Kynurenine plays an immunosuppressive role in 2,4,6-trinitrobenzene sulfate-induced colitis in mice.2020
Author(s)
Tashita C, Hoshi M, Hirata A, Nakamoto K, Ando T, Hattori T, Yamamoto Y, Tezuka H, Tomita H, Hara A, Saito K.
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Journal Title
World J Gastroenterol.
Volume: 26
Issue: 9
Pages: 918-932
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] The deficit of quinolinic acid phosphoribosyltransferase induces hypolocomotion and cognitive impairment through impairment of dopaminergic neuronal function2019
Author(s)
Moe Niijima, Akihiro Mouri, Tomoaki Teshigawara, Kazuo Kunisawa, Hisayoshi Kubota, Mami Hirakawa, Yuko Mori, Masato Hoshi, Yasuko Yamamoto, Toshitaka Nabeshima, Kuniaki Saito
Organizer
AsCNP
Related Report
Int'l Joint Research
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