Novel Therapeutic Approach Targeting CXCR3 to Treat Immunotherapy Myocarditis.

• Tác giả: Pilar Alcaide, Abraham L Bayer, Gerald J Berry, Corynn Branche, Harrison Chou, Edward E Graves, Yuhsin Vivian Huang, Daniel Lee, Zachary Lin, Joel W Neal, Patricia K Nguyen, Yin Sun, Maria Rosaria Vitale, Noah Wagner, Heather A Wakelee, Sarah Waliany, Ronald M Witteles, Sean M Wu, Bruce Xu, Han Zhu
• Ngôn ngữ: eng
• Ký hiệu phân loại: 362.178 Therapeutic services
• Thông tin xuất bản: United States : Circulation research , 2025
• Bộ sưu tập: NCBI
• ID: 52100

Tóm tắt

BACKGROUND: Immune checkpoint inhibitors (ICIs) are successful in treating many cancers but may cause immune-related adverse events. ICI-mediated myocarditis has a high fatality rate with severe cardiovascular consequences. Targeted therapies for ICI myocarditis are currently limited. METHODS: We used a genetic mouse model of PD1 deletion ( RESULTS: Single-cell multiomics demonstrated expansion of CXCL (C-X-C motif chemokine ligand) 9/10+CCR2+ macrophages and CXCR3hi (C-X-C motif chemokine receptor 3 high-expressing) CD8+ (cluster of differentiation) effector T lymphocytes in the hearts of CONCLUSIONS: These findings bring forth the CXCR3-CXCL9/10 axis as an attractive therapeutic target for ICI myocarditis treatment, and more broadly as a druggable pathway in cardiac inflammation.