2019 Fiscal Year Final Research Report
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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| 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 |
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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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| Free Research Field |
腫瘍免疫学
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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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