Relationship between Immune Checkpoint Inhibitors and Myocarditis

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Relationship between Immune Checkpoint Inhibitors and Myocarditis


Shihori Tanabe*

Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan

*Corresponding author: Tanabe S, Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, Kawasaki 210-9501, Japan

Citation: Tanabe S. (2022) Relationship between Immune Checkpoint Inhibitors and Myocarditis. Adv Clin Med Res. 3(4):1-2.

Received: October 12,  2022 | Published: October 20, 2022

Copyright© 2022 genesis pub by Tanabe S. CC BY-NC-ND 4.0 DEED. This is an open-access article distributedunder the terms of the Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License.,This allows others distribute, remix, tweak, and build upon the work, even commercially, as long as they credit the authors for the original creation.



Immune checkpoint inhibitors (ICIs) induce anti-cancer immunity. Several reports have indicated that treatment with ICIs is involved in myocarditis. In this Editorial, the relationship between ICIs and myocarditis is reviewed. The ICIs include ipilimumab, which is an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, and nivolumab, pembrolizumab, and cemiplimab, which are anti-programmed cell death protein 1 (PD-1) antibodies, and avelumab, atezolizumab, and durvalumab, which are anti-programmed cell death-ligand 1 (PD-L1) antibodies. Myocarditis, defined as inflammation of the muscular walls of the heart, is induced by several infectious diseases and molecules. The investigation into ICI-related myocarditis is ongoing.


Cancer; Cancer treatment; Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4); Immune checkpoint inhibitor; Myocarditis; Programmed cell death protein 1 (PD-1)

Immune checkpoint inhibitors (ICIs) in cancer treatment and myocarditis

Immune checkpoint inhibitors (ICIs) have been approved for cancer treatment and it was reported to have some cases of ICI-related cardiotoxicity [1]. There are some sporadic cases of ICI-associated myocarditis [2]. ICI-induced myocarditis in cancer patients has been reported [3]. ICI-related myocarditis is associated with a high reported mortality [4]. A comprehensive review of ICI therapy and myocarditis has found that ICI therapy-related myocarditis occurs at an average age of 68 years, and the characteristics of the patients include higher incidence in men and pretreatment cardiac history of hypertension [5]. Especially, ICI therapy with nivolumab, an anti-programmed death protein 1 (PD-1) monoclonal antibody, had mortality in 51.9% [5].

Preclinical experiments revealed that heterozygous loss of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) gene in Pdcd1 (encoding PD-1)-knockout mice demonstrated cardiac immune infiltration, and abatacept, a recombinant CTLA4-immunoglobulin fusion, rescued the fatal myocarditis in the Ctla4+/- Pdcd1-/- mice [6]. A study of cardiovascular magnetic resonance in ICI-related myocarditis demonstrated that late gadolinium enhancement was present in less than 50% of patients examined [7]. Investigation of the mechanism behind ICI-induced myocarditis needs to be continued in terms of the molecular pathway and infection-induced immunity perspectives.


This work was supported by Japan Agency for Medical Research and Development (AMED), Grant Number JP21mk0101216, JP22mk0101216, JSPS KAKENHI Grant Number 21K12133, and Ministry of Health, Labour, and Welfare (MHLW). The author would like to acknowledge all collaborators.


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