Unraveling Immune Checkpoint Inhibitor-Associated Cardiovascular Toxicities: Pathway Insights, Mechanisms, and Emerging Therapeutic Targets

Immune checkpoints are critical regulatory molecules in the immune system that maintain self-tolerance by preventing excessive immune activation against healthy tissues while being exploited by malignant cells to promote tumorigenesis and metastasis through immune evasion mechanisms. Immune checkpoint inhibitors (ICIs), represented by programmed cell death protein-1 (PD-1) inhibitors, are a revolutionary class of antitumor therapeutics that have achieved remarkable clinical success over the last decade, with the application of ICIs expanding to a broader spectrum of malignancies. Nonetheless, the administration of ICIs may induce immune dysregulation, potentially leading to the development of multiple immune-related adverse events (irAEs) across various organ systems. Cardiovascular toxicities are a series of relatively rare but severe irAEs that are drawing increasing attention. This review summarizes the latest findings in immune checkpoint signaling pathways and the potential mechanisms underlying the development of various cardiovascular toxicities associated with immunotherapies. Additionally, we also evaluate advances and novel therapeutic targets in the treatment of cardiovascular toxicities.