Fibrotic Rewiring of CD8+ T Cells by Doxorubicin Drives Pathological Remodeling of Cardiac Extracellular Matrix

Background

Anthracycline chemotherapy can lead to cardiotoxicity and chronic heart failure, and specific preventative therapies are nonexistent to date. As such, mechanistic investigation is needed to develop cardioprotective strategies. We previously showed that the anthracycline doxorubicin elicits a cardiotropic CD8+ T-cell response that contributes to cardiac fibroblast transformation, fibrosis, and chronic cardiotoxicity. However, the exact molecular mechanisms of T-cell-induced fibrosis, and whether T cells can directly induce cardiac remodeling, remain unknown.