CHECKPOINT ATHERO

• Willem MULDER, Radboud University Medical Center (Nijmegen) (Netherlands)
• Esther LUTGENS, MAYO CLINIC (USA)

Immunotherapy has revolutionized the way cancer patients that were previously deemed incurable can be treated. Patients with solid tumors are now being successfully treated with antibodies against inhibitory immune checkpoints, underlining the widespread therapeutic potential of this class of immunomodulators. Immune checkpoint proteins are master regulators of inflammation and can propagate or halt immune-cell activation. Although immune checkpoint targeting has been rapidly integrated in oncology treatment, the exploitation in cardiovascular disease is in its infancy. The underlying cause of the majority of cardiovascular diseases is atherosclerosis, a lipid-driven chronic inflammatory disease that affects mid- and large-sized arteries. Due to the formation of atherosclerotic plaques, life-threatening atherothrombotic events, including myocardial infarction or stroke, may arise when these plaques rupture or erode. Recent clinical trials have revealed that lowering inflammation is an important strategy to combat cardiovascular disease. However, these anti-inflammatory immunotherapies were not developed specifically for cardiovascular disease and therefore exhibited suboptimal efficacy and induced unwanted side effects, including infections. The CHECKPOINT ATHERO consortium is a Leducq International Network of Excellence that will explore the potential of immune checkpoint therapy for atherosclerosis. Our team has identified 5 candidate immune checkpoints: CD40, OX40L, CD200, GITR and VISTA, and will characterize the unique signature of these immune checkpoints in human atherosclerosis and its relationship with cardiovascular disease risk. We will identify underlying regulatory mechanisms of our candidate immune checkpoints in atherosclerosis and assess novel interventional approaches to combat cardiovascular disease. This network will bring together expert clinical investigators in the fields of inflammation and atherosclerosis with leading investigators in the fields of vascular biology, immunology, antibody development and nano-immunotherapy.