Development of novel treatment for fulminant myocarditis focusing on immune checkpoint molecules

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K23843
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0803:Pathology, infection/immunology, and related fields
• Research Institution: Nagoya University
• Principal Investigator: Hiraiwa Hiroaki 名古屋大学, 医学部附属病院 循環器内科, 病院助教 (10844904)
• Project Period (FY): 2019-08-30 – 2023-03-31
• Keywords: 劇症型心筋炎 / リンパ球性心筋炎 / 免疫チェックポイント分子 / PD-1, PD-L1 / 活性化T細胞 / 予後

Outline of Final Research Achievements

This study investigated the relationship between T cell markers and PD-L1 expression in myocardial tissue and the prognosis of patients with fulminant lymphocytic myocarditis (FM). We analyzed 16 FM patients and found that the number of CD8+ T cells and CD8+/CD4+ T cell ratio were significantly higher in the group with cardiac events (composite of cardiac death and left ventricular assist device implantation). Additionally, the number of FoxP3+ T cells was higher in the cardiac event group, and PD-L1 expression in myocardial cells was also higher in the same group. Kaplan-Meier survival analysis revealed that high CD8+ T cell count or high PD-L1 expression in the myocardium could be poor prognostic factors in FM. Combining the expression of CD8+ T cells and PD-L1 could potentially help stratify the risk of cardiac events in FM. This study provides new insights into the mechanism and prognosis of fatal FM, which could aid in the development of new treatment strategies in the future.

Free Research Field

重症心不全

Academic Significance and Societal Importance of the Research Achievements

リンパ球性劇症型心筋炎（FM）は致死的な疾患であり、劇症化メカニズムや治療開発に対する社会的ニーズが非常に高い。本研究では、T細胞プロファイルおよび免疫チェックポイント分子であるPD-1およびPD-L1の発現に注目した。結果、FM患者のうち、CD8陽性T細胞数およびCD8陽性/CD4陽性T細胞比が高い群で予後が悪いこと、PD-L1高発現群やCD8高値-PD-L1高発現群で生存率が低く、CD8陽性T細胞とPD-L1の発現を組み合わせることで、予後層別化が可能であることを示した。本研究の結果は、FM患者の予後を予測するための新たな知見を提供し、将来的に新たな治療戦略の開発に役立つことが期待される。