Myocarditis Induced by Immune Checkpoint Inhibitors: Mechanisms and Therapeutic Prospects

Abstract

Wenlu Zou,1– 3,* Jie Lu,4,* Yan Hao5 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, 250021, People’s Republic of China; 2Department of Infectious Disease; 3Department of Clinical Laboratory, Shandong University Qilu Hospital, Jinan, Shandong Province, 250012, People’s Republic of China; 4Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Neurosurgery, Jinan, 250117, Shandong Province, People’s Republic of China; 5Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Hao Email [email protected]: Under physiological conditions, immune checkpoint molecules downregulate the activation and effector function of myocardial antigen-reactive T cells through an immunosuppressive pathway, thus enabling myocardial T cells to maintain immune homeostasis under the action of central and peripheral tolerance mechanisms. The PD-1/PD-L1 signalling pathway is particularly important for limiting the ability of T cells to attack the heart. Immune checkpoint inhibitors (ICIs) specifically block this PD-1/PD-L1-mediated restriction of T cell activation and other immunosuppressive pathways by targeting immune checkpoints. In recent years, with the wide use of ICIs in cancer treatment, even though the incidence of immunomyocarditis is low, it has attracted increasing attention because of its complex clinical symptoms, rapid progression of disease and high mortality rates. The pathogenesis, genetic susceptibility factors and predictive biomarkers of immunomyocarditis still need to be understood, and multidisciplinary cooperation in the clinical treatment of this complication is necessary.Keywords: immunomyocarditis, immune checkpoint inhibitors, anti-PD-1/PD-L1, cancer

Keywords

• immunomyocarditis
• immune checkpoint inhibitors
• anti-pd-1/pd-l1
• cancer