Inhibition of Programmed Cell Death-1 in Cytotoxic CD8(+) T Cells Exacerbates Pressure Overload-Induced Cardiac Injury.

Blocking PD-1 in CD8(+) T cells worsens pressure overload-induced heart failure by increasing mitochondrial damage and cardiomyocyte death, with a 2.5-fold increase in severity.

• Why it matters: Understanding how immune checkpoint inhibition affects cardiac injury is crucial, as anti-PD-1 therapies are linked to increased heart failure risk in cancer patients with preexisting cardiovascular issues.
• What they did: The study used genetic and pharmacological methods to inhibit PD-1 in mice subjected to pressure overload, analyzing immune cell infiltration, chemotaxis, and mitochondrial function through flow cytometry, Western blotting, and RNA sequencing.
• The result: Findings reveal that PD-1 blockade enhances CXCR3+ CD8(+) T cell infiltration via CXCL9/CXCL10 signals, leading to granzyme B-mediated mitochondrial impairment and worsening heart failure, suggesting new targets to prevent cardiotoxicity.