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Article: Immunopathogenesis of Immune Checkpoint Inhibitor Induced Myocarditis: Insights from Experimental Models and Treatment Implications

TitleImmunopathogenesis of Immune Checkpoint Inhibitor Induced Myocarditis: Insights from Experimental Models and Treatment Implications
Authors
Keywordsautoimmunity
cancer
immune checkpoint inhibitor
immunotherapy
leukocyte
myocarditis
transgenic mice
Issue Date2023
Citation
Biomedicines, 2023, v. 11, n. 1, article no. 107 How to Cite?
AbstractDespite the extraordinary success of immune checkpoint inhibitors (ICIs) in cancer treatment, their use is associated with a high incidence of immune-related adverse events (IRAEs), resulting from therapy-related autoimmunity against various target organs. ICI-induced myocarditis is one of the most severe forms of IRAE, which is associated with risk of hemodynamic compromise and mortality. Despite increasing recognition and prompt treatment by clinicians, there remain significant gaps in knowledge regarding the pathophysiology, diagnosis and treatment of ICI-induced myocarditis. As the newly emerged disease entity is relatively rare, it is challenging for researchers to perform studies involving patients at scale. Alternatively, mouse models have been developed to facilitate research understanding of the pathogenesis of ICI-induced myocarditis and drug discovery. Transgenic mice with immune checkpoint genes knocked out allow induction of myocarditis in a highly reproducible manner. On the other hand, it has not been possible to induce ICI-induced myocarditis in wild type mice by injecting ICIs monotherapy alone. Additional interventions such as combinational ICI, tumor inoculation, cardiac sarcomere immunization, or cardiac irradiation are necessary to mimic the underlying pathophysiology in human cancer patients and to induce ICI-induced myocarditis successfully. This review focuses on the immunopathogenesis of ICI-induced myocarditis, drawing insights from human studies and animal models, and discusses the potential implications for treatment.
Persistent Identifierhttp://hdl.handle.net/10722/325594
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, Chun Ka-
dc.contributor.authorLam, Tsun Ho-
dc.contributor.authorLiao, Song Yan-
dc.contributor.authorLau, Yee Man-
dc.contributor.authorTse, Hung Fat-
dc.contributor.authorSo, Benjamin Y.F.-
dc.date.accessioned2023-02-27T07:34:37Z-
dc.date.available2023-02-27T07:34:37Z-
dc.date.issued2023-
dc.identifier.citationBiomedicines, 2023, v. 11, n. 1, article no. 107-
dc.identifier.urihttp://hdl.handle.net/10722/325594-
dc.description.abstractDespite the extraordinary success of immune checkpoint inhibitors (ICIs) in cancer treatment, their use is associated with a high incidence of immune-related adverse events (IRAEs), resulting from therapy-related autoimmunity against various target organs. ICI-induced myocarditis is one of the most severe forms of IRAE, which is associated with risk of hemodynamic compromise and mortality. Despite increasing recognition and prompt treatment by clinicians, there remain significant gaps in knowledge regarding the pathophysiology, diagnosis and treatment of ICI-induced myocarditis. As the newly emerged disease entity is relatively rare, it is challenging for researchers to perform studies involving patients at scale. Alternatively, mouse models have been developed to facilitate research understanding of the pathogenesis of ICI-induced myocarditis and drug discovery. Transgenic mice with immune checkpoint genes knocked out allow induction of myocarditis in a highly reproducible manner. On the other hand, it has not been possible to induce ICI-induced myocarditis in wild type mice by injecting ICIs monotherapy alone. Additional interventions such as combinational ICI, tumor inoculation, cardiac sarcomere immunization, or cardiac irradiation are necessary to mimic the underlying pathophysiology in human cancer patients and to induce ICI-induced myocarditis successfully. This review focuses on the immunopathogenesis of ICI-induced myocarditis, drawing insights from human studies and animal models, and discusses the potential implications for treatment.-
dc.languageeng-
dc.relation.ispartofBiomedicines-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectautoimmunity-
dc.subjectcancer-
dc.subjectimmune checkpoint inhibitor-
dc.subjectimmunotherapy-
dc.subjectleukocyte-
dc.subjectmyocarditis-
dc.subjecttransgenic mice-
dc.titleImmunopathogenesis of Immune Checkpoint Inhibitor Induced Myocarditis: Insights from Experimental Models and Treatment Implications-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/biomedicines11010107-
dc.identifier.pmid36672615-
dc.identifier.pmcidPMC9855410-
dc.identifier.scopuseid_2-s2.0-85146785455-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. 107-
dc.identifier.epagearticle no. 107-
dc.identifier.eissn2227-9059-
dc.identifier.isiWOS:000914494800001-

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