The immune checkpoint regulator CD40 potentiates myocardial inflammation.

ABSTRACT: Immune checkpoint therapeutics including CD40 agonists have tremendous promise to elicit antitumor responses in patients resistant to current therapies. Conventional immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 antagonists) are associated with serious adverse cardiac events including life-threatening myocarditis. However, little is known regarding the potential for CD40 agonists to trigger myocardial inflammation or myocarditis. Here we leverage genetic mouse models, single-cell sequencing and cell depletion studies to show that an anti-CD40 agonist antibody reshapes the cardiac immune landscape through activation of CCR2⁺ macrophages and subsequent recruitment of effector memory CD8⁺ T cells. We identify a positive feedback loop between CCR2⁺ macro

SUBMITTER: Jimenez J 

PROVIDER: S-EPMC12641230 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature