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      The Balance of CD8-Positive T Cells and PD-L1 Expression in the Myocardium Predicts Prognosis in Lymphocytic Fulminant Myocarditis

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          Abstract

          Introduction

          The clinical significance and prognostic value of T cell involvement and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) have not been established in lymphocytic fulminant myocarditis (FM). We investigated the prognostic impact of the number of CD4 +, CD8 +, FoxP3 +, and PD-1 + T cells, as well as PD-L1 expression, in cardiomyocytes in lymphocytic FM.

          Methods

          This is a single-center observational cohort study. Myocardial tissue was obtained from 16 consecutive patients at lymphocytic FM onset. The median follow-up was 140 days. Cardiac events were defined as a composite of cardiac death and left ventricular-assist device implantation. CD4, CD8, FoxP3, PD-1, and PD-L1 immunostaining were performed on myocardial specimens.

          Results

          The median age of the patients was 52 years (seven men and nine women). There was no significant difference in the number of CD4 + cells. The number of CD8 + cells and the CD8 +/CD4 + T cell ratio were higher in the cardiac event group (Event+) than in the group without cardiac events (Event−) ( p = 0.048 and p = 0.022, respectively). The number of FoxP3 + T cells was higher in the Event+ group ( p = 0.049). Although there was no difference in the number of PD-1 + cells, cardiomyocyte PD-L1 expression was higher in the Event+ group ( p = 0.112). Event-free survival was worse in the group with a high CD8 + cell count ( p = 0.012) and high PD-L1 expression ( p = 0.049). When divided into three groups based on the number of CD8 + cells and PD-L1 expression (CD8 highPD-L1 high [ n = 8], CD8 lowPD-L1 high [ n = 1], and CD8 lowPD-L1 low [ n = 7]), the CD8 highPD-L1 high group demonstrated the worst event-free survival, while the CD8 lowPD-L1 high group had a favorable prognosis without cardiac events ( p = 0.041).

          Conclusion

          High myocardial expression of CD8 + T cells and PD-L1 may predict a poor prognosis in lymphocytic FM.

          Plain Language Summary

          Myocarditis is a heart condition caused by inflammation of the heart muscle. Fulminant myocarditis (FM) is a severe form that can lead to sudden heart failure, shock, or dangerous heart rhythms. Understanding how the immune system is involved in FM is crucial for finding better treatments. In this study, we examined heart tissue from 16 patients with lymphocytic FM to understand the role of specific immune cells (T cells) and molecules (PD-1 and PD-L1) in the disease. We followed the patients for about 5 months to track their outcomes. We found that patients with more CD8+ T cells (a type of immune cell) in their heart tissue had a higher risk of cardiac events such as heart failure. Furthermore, when a specific molecule called PD-L1 was more abundant in heart cells, it indicated a poorer prognosis. This suggests that high levels of CD8+ T cells and PD-L1 in the heart tissue can predict a worse outcome for patients with lymphocytic FM. Understanding these markers may help doctors identify patients at higher risk and tailor treatments to improve their prognosis. However, more research with larger groups of patients is needed to confirm these findings and guide treatment decisions.

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          Most cited references44

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          Atezolizumab and Nab-Paclitaxel in Advanced Triple-Negative Breast Cancer

          Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) breast cancer is an aggressive disease with poor outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.
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            Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial.

            Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.
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              Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.

              In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.
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                Author and article information

                Journal
                Cardiology
                Cardiology
                CRD
                CRD
                Cardiology
                S. Karger AG (Basel, Switzerland )
                0008-6312
                1421-9751
                12 October 2023
                February 2024
                : 149
                : 1
                : 28-39
                Affiliations
                [a ]Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [b ]Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan
                [c ]Center for Clinical Pathology, Fujita Health University Hospital, Toyoake, Japan
                [d ]Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, Nagoya, Japan
                [e ]Department of Pathology, Fujita Health University, Toyoake, Japan
                Author notes
                Correspondence to: Hiroaki Hiraiwa, hiraiwa.hiroaki@ 123456med.nagoya-u.ac.jp
                Article
                534518
                10.1159/000534518
                10836849
                37827123
                d9d34ddf-7f2e-4353-81fa-da09ffb15e7a
                © 2023 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution 4.0 International License (CC BY) ( http://www.karger.com/Services/OpenAccessLicense). Usage, derivative works and distribution are permitted provided that proper credit is given to the author and the original publisher.

                History
                : 29 May 2023
                : 3 October 2023
                : 2024
                Page count
                Figures: 3, Tables: 3, References: 44, Pages: 12
                Funding
                This research was supported in part by a Grant-in-Aid for Scientific Research of the Japan Society for the Promotion of Science (JSPS KAKENHI [Grant No. JP19K23843 to Hiroaki Hiraiwa]).
                Categories
                Cardiovascular Biomarkers: Research Article

                lymphocytic fulminant myocarditis,t cell,programmed cell death-1,programmed cell death ligand-1,prognosis

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