2021 Fiscal Year Final Research Report
Analysis of the mechanism of drug-induced lung injury focusing on immune checkpoint molecules
| Project/Area Number |
19K08654
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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 | Kyushu University |
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Principal Investigator |
Hamada Naoki 九州大学, 大学病院, 講師 (00423567)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 肺傷害 / 薬剤性間質性肺炎 / 上皮成長因子受容体チロシンキナーゼ阻害薬 / 免疫チェックポイント阻害薬 |
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| Outline of Final Research Achievements |
Expression of immune checkpoint molecules in lymphocytes in bronchoalveolar lavage fluid was analyzed in cases of interstitial lung diseaseThe expression of PD-1, TIM-3, and TIGIT was significantly elevated in cases of drug-induced pneumonia by ICI (Int Immunol. 2020). A similar trend was observed in MDA5 antibody-positive acute interstitial pneumonia (Rheumatology (Oxford). 2021). In sarcoidosis, PD-1 and TIM-3 expression was elevated in the spontaneous improvement group (Biomedicines 2021).
Combined use of EGFR-TKI in mouse naphthalene lung injury resulted in exacerbation of lung injury. Increases in neutrophils were observed with 1st and 2nd generation EGFR-TKIs, and increases in neutrophils and lymphocytes were observed with 3rd generation EGFR-TKI.
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| Free Research Field |
呼吸器病学
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| Academic Significance and Societal Importance of the Research Achievements |
薬剤性肺炎の機序は不明であるが一般的にリンパ球の上昇が認められる。今回、気管支肺胞洗浄液中のリンパ球が上昇する疾患として、薬剤性肺炎、膠原病間質性肺炎、サルコイドーシスにて免疫チェックポイント分子の解析と、T細胞活性化を示すことができた。また動物モデルでもリンパ球上昇を伴う薬剤性肺炎モデルができつつある。これらの解析が、薬剤性肺傷害の発症予測、治療法の開発への大きな第一歩となりうる
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