Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies

Area of Science:

• Oncology
• Immunology
• Cardiology

Background:

• Immune checkpoint inhibitors (ICIs), particularly those targeting the PD-1/PD-L1 axis, have transformed cancer treatment.
• Recent FDA approvals highlight the growing use of PD-1/PD-L1 blocking antibodies across various cancer types.
• Immune-related adverse events (IRAEs), including severe cardiac effects like myocarditis, are significant concerns associated with these therapies.

Purpose of the Study:

• To systematically review the pathophysiology of the PD-1/PD-L1 axis and its associated cardiac effects.
• To explore cardiac IRAEs in pre-clinical models, clinical trials, and in combination with other cancer treatments.
• To discuss current diagnostic challenges and future directions for managing cardiac complications of immunotherapy.

Main Methods:

• Systematic review of literature on PD-1/PD-L1 axis and cardiac effects.
• Analysis of pre-clinical models, clinical trial data, and autoimmune mechanisms.
• Review of immunotherapy combinations and diagnostic challenges.

Main Results:

• The underlying mechanisms of ICI-induced myocarditis remain largely unknown despite clinical observations.
• Current management strategies involve corticosteroids, which can compromise cancer treatment efficacy.
• The review synthesizes existing knowledge on PD-1/PD-L1 pathways and cardiac adverse events.

Conclusions:

• Understanding the mechanisms of cardiac IRAEs is critical for developing effective prevention and treatment strategies.
• Early detection and novel therapeutic approaches are needed to mitigate the risks of immunotherapy-related cardiac toxicity.
• This review provides a comprehensive overview to guide future research and clinical practice in managing these adverse events.