Immune Checkpoint Inhibitors and Atherosclerotic Vascular Events in Cancer Patients

Abstract

In clinical trials and meta-analysis, atherosclerotic vascular events (AVEs) during treatment with immune-checkpoint inhibitors (ICIs) have been reported with low incidence. However, preclinical data suggest that these drugs can promote atherosclerosis inflammation and progression of atherosclerosis plaques, and there is now growing and convincing evidence from retrospective studies that ICIs increase the risk of atherosclerotic vascular events including arterial thrombosis, myocardial infarction and ischemic stroke. Prospective studies are needed to increase knowledge on long-term effect of ICIs or their combinations with other cardio-toxic drugs, but in the meantime a careful assessment and optimization of cardiovascular risk factors among patients treated with ICIs is advisable.

Keywords: CTLA-4; PD-1; PD-L1; acute vascular events; arterial thrombosis; atherosclerosis; ischemic stroke; myocardial infarction.

Figure 1

Role of PD-1 and PD-1 blockade in the homeostasis of atherosclerotic plaque. Left side: Binding of PD-1 expressed on T-cells with PD-L1/PD-L2 expressed on DCs and in microenvironment contribute to the inactivation of T-cells and to the maintenance of an immunosuppressive plaque microenvironment. Right side: Anti-PD-1 leads to T-cells activation with production of proinflammatory cytokines such as TNF-α and IFNγ. TNF-α and IFNγ promote smooth muscle cell proliferation, collagen deposition and activation of macrophages that increase the phagocytosis of LDL with transformation into foam cells (8, 9). These changes in the plaque structure ultimately lead to the formation of a necrotic core and plaque instability (Picture created with Biorender.com).