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      Managing cardiotoxicity associated with immune checkpoint inhibitors

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          Abstract

          Immuno-oncology is a fast evolving field of cancer therapy and immune checkpoint inhibitors (ICIs) are clearly a breakthrough in this field. Cardiotoxicity with conventional anti-cancer therapies has been well studied in the past and clear guidelines for management of these side effects are available in the literature. However, cardiotoxicity with novel agents such as ICIs has been fairly under-reported and/or underestimated and we are yet to formulate clear guidelines for management of these rare side effects. In the last few years, there has been an overall increase in the number of cases of cardiotoxicity related to ICIs. In this literature review, we describe the mechanism of action of the most widely used ICIs and their related cardiotoxicities. The increase in number of case reports about the potential of cardiotoxicities with these novel agents clearly indicates the need for a new insight into the field of cardio-immuno-oncology.

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          Most cited references35

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          Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4.

          The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.
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            Immune checkpoint inhibitors and cardiovascular toxicity

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              Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity.

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                Author and article information

                Contributors
                Journal
                Chronic Dis Transl Med
                Chronic Dis Transl Med
                Chronic Diseases and Translational Medicine
                Chinese Medical Association
                2095-882X
                2589-0514
                21 March 2019
                March 2019
                21 March 2019
                : 5
                : 1
                : 6-14
                Affiliations
                [a ]Department of Internal Medicine, Saint Agnes Hospital, Baltimore, MD 21229, USA
                [b ]Department of Internal Medicine, University of Maryland, Baltimore, MD 21201, USA
                [c ]Departments of Oncology and Surgery, The Pancreatic Cancer Precision Medicine Center of Excellence Program, The Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD 21287, USA
                Author notes
                []Corresponding author. 1650 Orleans Street, CRB1, Room 351, Baltimore, MD 21287, USA. Fax: +1 410 614 8217. lzheng6@ 123456jhmi.edu
                Article
                S2095-882X(18)30111-7
                10.1016/j.cdtm.2019.02.004
                6450824
                30993259
                45a6e0de-3ee9-484c-9f17-15e6c89b9314
                © 2019 Chinese Medical Association. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 December 2018
                Categories
                Perspective

                immune checkpoint inhibitor,cardiotoxicity,ipilimumab,nivolumab,pembrolizumab

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