Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis: Therapeutic Targets in Atherosclerosis?

Area of Science:

• Cardiovascular Medicine
• Immunology
• Pharmacology

Background:

• Current treatments for atherosclerotic cardiovascular disease (ASCVD) primarily focus on managing cardiovascular risk factors like hyperlipidemia, with recent advances including PCSK-9 inhibitors.
• Emerging evidence highlights inflammation as a significant driver of atherosclerosis, necessitating exploration beyond lipid-lowering therapies.
• While clinical trials targeting inflammation in ASCVD have shown promise in patient tolerance, reduced inflammatory markers, and improved cardiovascular endpoints, optimal strategies are still under investigation.

Purpose of the Study:

• To review the potential of immune checkpoint-based therapeutics as a novel immunotherapeutic strategy for treating atherosclerotic cardiovascular disease (ASCVD).
• To discuss the application of costimulation and coinhibition immune checkpoint inhibitors, many of which are FDA-approved for cancer and autoimmune diseases, in the context of ASCVD treatment.

Main Methods:

• Review of existing clinical trial data (Phase 1, 2, and 3) on anti-inflammatory therapies for ASCVD.
• Analysis of experimental evidence linking inflammation to atherosclerosis.
• Focus on immune checkpoint inhibitors (costimulation and coinhibition) and their established uses in other diseases.

Main Results:

• Clinical trials indicate that immune-modulating therapies for ASCVD are generally well-tolerated by patients.
• These therapies have demonstrated reductions in key inflammatory markers.
• Some trials have shown positive impacts on cardiovascular endpoints, although further research is needed.

Conclusions:

• Atherosclerosis is driven by inflammation, suggesting a role for immunotherapies beyond traditional risk factor management.
• Immune checkpoint inhibitors represent a promising novel therapeutic avenue for ASCVD, leveraging existing approvals for other conditions.
• Further research is required to identify optimal immune-based strategies and patient stratification for ASCVD treatment.