阿霉素是最常用的化疗药物，会引起剂量依赖性心脏毒性和心力衰竭。然而，我们对阿霉素引起的免疫反应的了解是有限的。在这里，我们发现阿霉素诱导的心脏损伤后异常的 CD8 T 细胞免疫反应会导致不良重塑和心肌病。对非荷瘤小鼠进行阿霉素治疗可增加淋巴组织中循环和心脏 IFNγ CD8 T 细胞以及激活的效应 CD8 T 细胞。此外，阿霉素可促进阿霉素治疗小鼠心脏 CD8 T 细胞浸润和 CD8 T 细胞耗竭，从而减少心脏纤维化并改善收缩功能。阿霉素治疗诱导心脏成纤维细胞表达 ICAM-1，从而增强 CD8 T 细胞粘附和转化、接触依赖性 CD8 脱颗粒和颗粒酶 B 的释放。犬淋巴瘤患者和患有造血系统恶性肿瘤的人类患者在阿霉素治疗后显示出循环 CD8 T 细胞增加。在人类癌症患者中，T 细胞表达 IFNγ 和 CXCR3，CXCR3 配体 CXCL9 和 CXCL10 的血浆水平与收缩功能下降相关。© 2024。作者，获得 Springer Nature Limited 的独家许可。

Doxorubicin, the most prescribed chemotherapeutic drug, causes dose-dependent cardiotoxicity and heart failure. However, our understanding of the immune response elicited by doxorubicin is limited. Here we show that an aberrant CD8+ T cell immune response following doxorubicin-induced cardiac injury drives adverse remodeling and cardiomyopathy. Doxorubicin treatment in non-tumor-bearing mice increased circulating and cardiac IFNγ+CD8+ T cells and activated effector CD8+ T cells in lymphoid tissues. Moreover, doxorubicin promoted cardiac CD8+ T cell infiltration and depletion of CD8+ T cells in doxorubicin-treated mice decreased cardiac fibrosis and improved systolic function. Doxorubicin treatment induced ICAM-1 expression by cardiac fibroblasts resulting in enhanced CD8+ T cell adhesion and transformation, contact-dependent CD8+ degranulation and release of granzyme B. Canine lymphoma patients and human patients with hematopoietic malignancies showed increased circulating CD8+ T cells after doxorubicin treatment. In human cancer patients, T cells expressed IFNγ and CXCR3, and plasma levels of the CXCR3 ligands CXCL9 and CXCL10 correlated with decreased systolic function.© 2024. The Author(s), under exclusive licence to Springer Nature Limited.