Targeting ligand PDL1 for cardiotoxicity assessment and cardiac protection in immune-related myocarditis

作者：Yi Li, Xiaoxin Li, Fei Liu, Huan Zhang, Jing Guo, Guangcheng Liu, Jiaxin Wang, Qing Zhong, Qun Liu, Lulu Liu, Peijun Liu, Weifang Cao, Yingxian Liu, Xin Zhang, Haiming Fan, Zhuoli Zhang, Yining Wang · 发表于：Nanomedicine · 年份：2025 · DOI：10.1080/17435889.2025.2595118 · 被引用次数：1 · 研究领域：Viral Infections and Immunology Research、Cardiac Fibrosis and Remodeling、Atherosclerosis and Cardiovascular Diseases

AIMS: The role of cardiac programmed cell death ligand 1 (PDL1) in immune checkpoint inhibitor (ICI) - related myocarditis (irMyocarditis) remains unclear. We aimed to investigate whether ligand PDL1 could serve as an early indicator and a potential therapeutic target for irMyocarditis. METHODS: Cardiac PDL1 expression was assessed using single-nucleus RNA sequencing and multiplex immunohistochemistry in human patients and mouse models of irMyocarditis. A PDL1-targeted magnetic resonance imaging (MRI) nanoprobe was developed for noninvasive imaging of irMyocarditis. Additionally, an adeno-associated virus 9 (AAV9) vector was employed to deliver the PDL1 gene to cardiomyocytes, and its therapeutic effects on irMyocarditis were evaluated in a mouse model. RESULTS: PDL1 expression was significantly elevated in the myocardium of irMyocarditis patients and mouse models. The PDL1-targeted MRI nanoprobe successfully detected myocarditis in vivo, with enhanced cardiac signals observed in affected mice compared to isotype controls. Therapeutic intervention using AAV9-mediated PDL1 gene delivery significantly reduced immune cell infiltration and cardiomyocyte apoptosis, improving left ventricular ejection fraction over a 2-month follow-up period. CONCLUSIONS: This study identifies PDL1 as a critical biomarker and therapeutic target for irMyocarditis. PDL1-targeted MRI nanoprobe enables early, noninvasive diagnosis, while AAV9-mediated PDL1 gene therapy offers a promising strategy to mi...