Pathogenesis of drug-induced pneumonitis with osimertinib and immune checkpoint inhibitors

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20889
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Kyushu University
• Principal Investigator: Tsubouchi Kazuya 九州大学, 大学病院, 助教 (60961927)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 薬剤性肺炎 / EGFRチロシンキナーゼ阻害薬

Outline of Final Research Achievements

The epidermal growth factor receptor tyrosine kinase inhibitor (osimertinib), widely used as a therapeutic agent for lung cancer, is associated with the development of drug-induced pneumonitis, leading to fatal outcomes. In this study, we investigated the pathogenesis of osimertinib-induced pneumonitis. Osimertinib was administered to mice, resulting in drug-induced pneumonitis similar to that observed in patients with osimertinib-induced pneumonitis, characterized by infiltration of immune cells called lymphocytes into the lungs. These lymphocytes are induced by cytokines secreted from the mouse's bronchial epithelium. This indicates that lymphocytes induced by damaged airway epithelium play a role in the pathophysiology of osimertinib-induced interstitial pneumonitis.

Free Research Field

呼吸器内科学

Academic Significance and Societal Importance of the Research Achievements

上皮成長因子受容体(epithelial growth factor receptor: EGFR)チロシンキナーゼ阻害薬は、肺癌の予後を大きく改善したが、一定の頻度で薬剤性間質性肺炎を発症し致死的な転機を取るため、薬剤性間質性肺炎の病態解明が求められている。本研究による結果はEGFRチロシンキナーゼ阻害薬による薬剤性肺炎の病態の一部を解明し、病態に関係するリンパ球を同定したことは薬剤性肺炎の診断や新規治療法の開発につながると考えられる。