Immune checkpoint proteins: exploring their therapeutic potential to regulate atherosclerosis

The immune system provides a large variety of immune checkpoint proteins, which involve both costimulatory and inhibitory proteins. Costimulatory proteins can promote cell survival, cell cycle progression and differentiation to effector and memory cells, whereas inhibitory proteins terminate these processes to halt ongoing inflammation. Immune checkpoint proteins play a pivotal role in atherosclerosis by regulating the activation and proliferation of various immune and non-immune cells, such as T-cells, macrophages and platelets. Upon activation within the atherosclerotic lesions or in secondary lymphoid organs, these cells produce large amounts of pro-atherogenic cytokines that contribute to the growth and destabilization of lesions, which can result in rupture of the lesion causing acute coronary syndromes, such as a myocardial infarction. Given the presence and regulatory capacity of immune checkpoint proteins in the circulation and atherosclerotic lesions of cardiovascular patients, modulation of these proteins by, for example, the use of monoclonal antibodies, offers unique opportunities to regulate pro-inflammatory immune responses in atherosclerosis. In this review, we highlight the latest advances on the role of immune checkpoint proteins, such as OX40-OX40L, CTLA-4 and TIM proteins, in atherosclerosis and discuss their therapeutic potential as promising immunotherapies to treat or prevent cardiovascular disease.