免疫チェックポイント阻害剤関連心筋炎の新規病態モデル開発

• Published in: 日本薬理学会年会要旨集 p. YIA05-2
• Main Authors: 新村, 貴博, 運天, 拡人, 濱野, 裕章, 内田, 和志, 友近, 七海, 宮田, 晃志, 合田, 光寛, 八木, 健太, 相澤, 風花, 石澤, 有紀, 座間味, 義人, 石澤, 啓介
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: heart; immune system
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.96.0_YIA05-2

Immune Checkpoint Inhibitors (ICI) show anti-tumor activity against various types of cancer, but they also disrupt the balance of the immune system and cause autoimmune-like adverse events. ICI-related myocarditis, in particular, has a fatality rate of over 40%, making the development of preventive and therapeutic agents an urgent priority. In present study, we developed a simple and reproducible experimental model for ICI-associated myocarditis.Myocardial myosin peptide (50 µg) was administered subcutaneously to male, 8-week-old BALB/c wild-type and PD-1KO mice at day 0 and 7. Three weeks after the initial myosin administration, the development of myocarditis was evaluated. HE staining and Masson trichrome staining showed inflammatory cell infiltration and fibrosis in myocardial tissue in myosin peptide-treated PD-1 KO mice. Next, the involvement of CD4⁺ and CD8⁺ cells was examined by immunostaining, and the infiltration of CD4⁺ and CD8⁺ cells was confirmed in the hearts of myosin-treated PD-1KO mice. Finally, the results of real-time PCR showed that myosin administration tended to increase gene expression of inflammatory cytokines and fibrosis markers in the hearts of PD-1KO mice.It is expected that this model will be used to develop new prophylactic and therapeutic agents for ICI-associated myocarditis.