PD-1 Blockade Worsens Pressure Overload–Induced Cardiac Injury in Mice

Researchers investigated mechanisms of anti–PD-1-associated cardiac injury using transverse aortic constriction to induce pressure overload in mice. Experiments combined anti–PD-1 antibody treatment, cell-specific Pdcd1 deletion, and genetic or pharmacological targeting of CXCR3 and granzyme B. Assessments addressed cardiac remodeling, heart failure, immune-cell infiltration, and mitochondrial injury. Sample sizes and numerical effect estimates were not provided in the available abstract.

Anti–PD-1 treatment and T-cell- or CD8+ T-cell-specific Pdcd1 deletion worsened cardiomyopathy and heart failure; myeloid-specific deletion did not. PD-1 blockade increased myocardial infiltration by CXCR3+ CD8+ T cells, recruited through cardiac fibroblast-derived CXCL9/CXCL10. Granzyme B/perforin-mediated impairment of cardiomyocyte mitochondrial complex I was implicated in the resulting injury. Genetic deletion or pharmacological blockade of granzyme B or CXCR3 rescued the worsened cardiac phenotype.

These findings identify a potential mechanism connecting PD-1 inhibition with cardiac vulnerability under pressure overload and suggest targets for further investigation. However, this was an experimental mouse study, not a clinical evaluation of cardiotoxicity prevention. The abstract does not establish whether targeting this pathway would protect patients or preserve anticancer efficacy; full text was unavailable for assessment.