Central Illustration.

Effects of Immune Checkpoint Alterations

Immune checkpoint inhibitors (ICIs) cause an enhanced immune response and persistent inflammation. Several pathways are being implicated in post-ICI aggravated atherosclerosis, with the strongest evidence for the co-inhibitory blockade via the cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) and the co-stimulatory agonism of CD40/CD40L and glucocorticoid-induced tumor necrosis factor family-related protein (GITR) pathways. Costimulatory molecules were B7.1= CD80 and B7.2 = CD86. APC = antigen-presenting cell; GITRL = glucocorticoid-induced tumor necrosis factor family-related protein ligand; ICAM= intracellular adhesion molecule; ICOS = inducible costimulatory; IFN = interferon; IL = interleukin; LAG-3 = lymphocyte activation gene 3; MHC = major histocompatibility complex; MI = myocardial infarction; MMP = matrix metalloproteinase; NK = natural killer; SIRP = signal-regulatory protein; TCR = T cell receptor; TGF = transforming growth factor; Th1 = T helper 1; TIM-3 = T cell immunoglobulin and mucin containing domain-3; TNF = tumor necrosis factor; Treg = regulatory T; VCAM = vascular cell adhesion molecule.