FIGURE 2.

Molecular mechanisms of cardiotoxicity induced by PD-1/PD-L1 blockade. B and T cells are activated by PD-1 or PD-L1 inhibitors. Macrophages, CD4⁺ and CD4⁺ T cells then infiltrate the myocardial tissue. In addition to the induction of inflammation and fibrosis by activating NF-κB and TGF-β1 signaling pathway, PDL-1 inhibitors induce the production of ROS by suppressing nuclear factor erythroid 2-related factor-2 (Nrf-2) and upregulating transcriptional factor forkhead box-1 (FOXO-1). PD-1 inhibitors also activate macrophages and induce the expression of proinflammatory cytokines by regulating the expression of miRNAs.