Association between Immune Checkpoint Inhibitors and Atherosclerotic Cardiovascular Disease Risk: Another Brick in the Wall

Abstract

In recent years, immune checkpoint inhibitors have significantly changed the field of oncology, emerging as first-line treatment, either alone or in combination with other regimens, for numerous malignancies, improving overall survival and progression-free survival in these patients. However, immune checkpoint inhibitors might also cause severe or fatal immune-related adverse events, including adverse cardiovascular events. Initially, myocarditis was recognized as the main immune checkpoint inhibitor-related cardiac event, but our knowledge of other potential immune-related cardiovascular adverse events continues to broaden. Recently, preclinical and clinical data seem to support an association between immune checkpoint inhibitors and accelerated atherosclerosis as well as atherosclerotic cardiovascular events such as cardiac ischemic disease, stroke, and peripheral artery disease. In this review, by offering a comprehensive overview of the pivotal role of inflammation in atherosclerosis, we focus on the potential molecular pathways underlying the effects of immune checkpoint inhibitors on cardiovascular diseases. Moreover, we provide an overview of therapeutic strategies for cancer patients undergoing immunotherapy to prevent the development of cardiovascular diseases.

Keywords: atherosclerosis; atherosclerotic cardiovascular events; cancer; cardiac event; cardiotoxicity; immune checkpoint inhibitors; immunotherapy; inflammation.

Figure 1

Role of inflammation in atherosclerosis. APC, antigen-presenting cell; OX-LDL, oxidized low-density lipoprotein; TH, T-helper lymphocite; T-Reg; and T-regulatory lymphocyte.

Figure 2

Role of ICIs in plaque progression and atherosclerotic cardiovascular events. APC, antigen-presenting cell; MHC, major histocompatibility complex.

Figure 3

PCSK9 impedes the recycling of MHC-I to the cell surface by facilitating MHC-I degradation. MHC-I, major histocompatibility complex I; PCSK-9, proprotein convertase substilisin/kexin type; and TCR, T-cell receptor.