2024-07-17 タフツ大学
<関連情報>
- https://now.tufts.edu/2024/07/17/why-most-prescribed-chemotherapy-drug-can-cause-serious-heart-damage
- https://www.nature.com/articles/s44161-024-00507-y
細胞傷害性T細胞がドキソルビシン誘発の心線維症と収縮機能障害を促進する Cytotoxic T cells drive doxorubicin-induced cardiac fibrosis and systolic dysfunction
Abraham L. Bayer,Maria A. Zambrano,Sasha Smolgovsky,Zachary L. Robbe,Abul Ariza,Kuljeet Kaur,Machlan Sawden,Anne Avery,Cheryl London,Aarti Asnani & Pilar Alcaide
Nature Cardiovascular Research Published:17 July 2024
DOI:https://doi.org/10.1038/s44161-024-00507-y
Abstract
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.
