2021 Fiscal Year Final Research Report
analysis of lung cancer immunotherapy targeting tryptophan metabolism
| Project/Area Number |
19K08667
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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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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Fujita Health University |
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Principal Investigator |
Kondo Masashi 藤田医科大学, 医学部, 教授 (00378077)
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| Co-Investigator(Kenkyū-buntansha) |
山本 直樹 藤田医科大学, 治験・臨床研究支援センター, 教授 (00267957)
星 雅人 藤田医科大学, 保健学研究科, 講師 (40633996)
今泉 和良 藤田医科大学, 医学部, 教授 (50362257)
佐藤 光夫 名古屋大学, 医学系研究科(保健), 教授 (70467281)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 肺癌 |
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| Outline of Final Research Achievements |
Kynurenine aminotransferase 1 (KAT1) is an enzyme that metabolizes 3-hydroxykynurenine, which is one of the tryptophan metabolites, to xanthurenic acid (XA). Administration of XA tended to activate tumor cell proliferation. Specific inhibition of K A T 1 by the drug suppressed tumor growth. It was also clarified that tryptophan itself inhibits KAT1. In lung cancer patients, there was a difference in KAT1 expression in proteins and mRNAs in lung adenocarcinoma tissue, and the survival rate was significantly lower in the KAT1 high expression group than in the low expression group. The response rate of anticancer drugs tended to be higher in the low serum XA group than in the high serum group.
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| Free Research Field |
肺癌
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍免疫に、トリプトファンの代謝物が関与することが示し、その中で、キサンツレン酸とそれに関連した酵素であるkynurenine aminotransferase １（KAT1）の重要性を見出した。これら成果により、現在の免疫チェックポイント阻害剤の治療の向上は図るために、この酵素を標的とした新規の腫瘍免疫併用療法の可能性を示唆できた。それを臨床応用するために、臨床研究の立案に着手できた。
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