Costimulatory and Coinhibitory Immune Checkpoints in Atherosclerosis

The benefits of current state-of-the-art treatments to combat atherosclerotic cardiovascular disease (ASCVD) have stagnated. Treatments are mostly based on controlling cardiovascular risk factors, especially hyperlipidemia. Although the most recent advances with PCSK-9 inhibitors support the hyperlipidemia aspect of ASCVD, several lines of experimental evidence have outlined that atherosclerosis is also driven by inflammation. In the past years, phase 1, 2, and 3 clinical trials targeting inflammation to combat ASCVD have revealed that patients do tolerate such immune therapies, show decreases in inflammatory markers, and/or have reductions in cardiovascular endpoints. However, the search for the optimal anti-inflammatory or immune-modulating strategy and the stratification of patients who would benefit from such treatments and appropriate treatment regimens to combat ASCVD is only just beginning. In this review, we focus on immune checkpoint–based therapeutics (costimulation and coinhibition), many of which are already approved by the U.S. Food and Drug Administration for the treatment of cancer or autoimmune diseases, and discuss their use as a novel immunotherapeutic strategy to treat ASCVD.