{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:46:39Z","timestamp":1793317599157,"version":"4.5.0"},"reference-count":69,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,22]],"date-time":"2021-05-22T00:00:00Z","timestamp":1621641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that activate the immune system, aiming at enhancing antitumor immunity. ICIs have shown great promise in the treatment of several advanced malignancies. However, therapy with these immunomodulatory antibodies may lead to a wide spectrum of immune-related adverse events in any organ and any tissue. Cardiologic immune-related events include pericarditis, pericardial effusion, various types of arrhythmias including the occurrence of complete atrioventricular block, myocardial infarction, heart failure, and myocarditis. Although relatively rare, myocarditis is associated with a very high reported mortality in comparison to other adverse events. Myocarditis often presents significant diagnostic complexity and may be under-recognized. When confronted with an unexpected change in the clinical picture, the physician must differentiate between immune-related adverse events, cancer worsening, or other causes unrelated to the cancer or its therapy. However, this is not always easy. Therefore, with the increasing use of checkpoint inhibitors in cancer, all providers who care for patients with cancer should be made aware of this rare, but potentially fatal, cardiologic immune-related adverse event, and able to recognize when prompt consultation with a cardiologist specialist is indicated. In this review, we evaluate currently available scientific evidence and discuss clinical manifestations and new potential approaches to the diagnosis and therapy of acute myocarditis induced by ICIs. Temporary or permanent discontinuation of the ICIs and high-dose steroids have been administered to treat myocarditis, but symptoms may worsen in some patients despite therapy.<\/jats:p>","DOI":"10.3390\/biom11060785","type":"journal-article","created":{"date-parts":[[2021,5,23]],"date-time":"2021-05-23T23:59:03Z","timestamp":1621814343000},"page":"785","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["An Emergent Form of Cardiotoxicity: Acute Myocarditis Induced by Immune Checkpoint Inhibitors"],"prefix":"10.3390","volume":"11","author":[{"given":"Roberta","family":"Esposito","sequence":"first","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"},{"name":"Mediterranea Cardiocentro, 80122 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Fedele","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Orefice","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3455-6168","authenticated-orcid":false,"given":"Vittoria","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Prastaro","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8452-7464","authenticated-orcid":false,"given":"Mario Enrico","family":"Canonico","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3885-5093","authenticated-orcid":false,"given":"Federica","family":"Ilardi","sequence":"additional","affiliation":[{"name":"Mediterranea Cardiocentro, 80122 Naples, Italy"},{"name":"Department of Advanced Biomedical Sciences, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Villa dei Fiori, 80011 Acerra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovica","family":"Fiorillo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-1680","authenticated-orcid":false,"given":"Ciro","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3322\/caac.21565","article-title":"Cancer treatment and survivorship statistics, 2019","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nrcardio.2015.65","article-title":"Cardiotoxicity of anticancer treatments","volume":"12","author":"Ewer","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1093\/eurheartj\/ehw211","article-title":"2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC)","volume":"37","author":"Zamorano","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0191-1","article-title":"Immune checkpoint inhibitors: Recent progress and potential biomarkers","volume":"50","author":"Darvin","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1200\/JCO.2014.59.4358","article-title":"Immune Checkpoint Blockade in Cancer Therapy","volume":"33","author":"Postow","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in Previously Untreated Melanoma without BRAF Mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1056\/NEJMoa1606774","article-title":"Pembrolizumab versus Chemotherapy for PD-L1\u2013Positive Non\u2013Small-Cell Lung Cancer","volume":"375","author":"Reck","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-019-0829-z","article-title":"Applications of patient-derived tumor xenograft models and tumor organoids","volume":"13","author":"Yoshida","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","first-page":"771","article-title":"Coverage Evaluation of CTCAE for Capturing the Im-mune-related Adverse Events Leveraging Text Mining Technologies","volume":"2019","author":"Yu","year":"2019","journal-title":"AMIA Jt. Summits Transl. Sci. Proc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal Toxic Effects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1056\/NEJMoa1609214","article-title":"Fulminant Myocarditis with Combination Immune Checkpoint Blockade","volume":"375","author":"Johnson","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jacc.2018.02.037","article-title":"Myocarditis in Patients Treated with Immune Checkpoint Inhibitors","volume":"71","author":"Mahmood","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/S0140-6736(18)30533-6","article-title":"Increased reporting of fatal immune checkpoint inhibi-tor-associated myocarditis","volume":"391","author":"Moslehi","year":"2018","journal-title":"Lancet"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1161\/CIRCULATIONAHA.117.030571","article-title":"Clinical Features, Manage-ment, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity","volume":"136","author":"Escudier","year":"2017","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.cjco.2020.11.004","article-title":"Plasma Ex-change for Immune Checkpoint Inhibitor-Induced Myocarditis","volume":"3","author":"Yogasundaram","year":"2020","journal-title":"CJC Open"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.ejca.2019.09.009","article-title":"A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies","volume":"124","author":"Guo","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_17","first-page":"6","article-title":"Managing cardiotoxicity associated with immune checkpoint inhibitors","volume":"5","author":"Upadhrasta","year":"2019","journal-title":"Chronic Dis. Transl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/S1470-2045(18)30608-9","article-title":"Cardiovascular toxicities associated with immune checkpoint inhibitors: An observational, retrospective, pharmacovigilance study","volume":"19","author":"Salem","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/S1470-2045(15)70122-1","article-title":"Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): A randomised, double-blind, phase 3 trial","volume":"16","author":"Eggermont","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1182\/blood.2019000324","article-title":"Pembrolizumab in relapsed or refractory Hodgkin lymphoma: 2-year follow-up of KEYNOTE-087","volume":"134","author":"Chen","year":"2019","journal-title":"Blood"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1016\/S0140-6736(16)00587-0","article-title":"Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): A multicentre, open-label, phase 2 randomised controlled trial","volume":"387","author":"Fehrenbacher","year":"2016","journal-title":"Lancet"},{"key":"ref_22","first-page":"68","article-title":"Myocarditis associated with immune checkpoint inhibitors: Practical considerations in diagnosis and management","volume":"24","author":"Yalta","year":"2020","journal-title":"Anatol. J. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1634\/theoncologist.2019-0555","article-title":"Immune Checkpoint Inhibi-tor-Associated Primary Adrenal Insufficiency: WHO VigiBase Rep","volume":"25","author":"Grouthier","year":"2020","journal-title":"Anal. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.4049\/jimmunol.181.4.2513","article-title":"Programmed Death Ligand 1 Regulates a Critical Checkpoint for Autoimmune Myocarditis and Pneumonitis in MRL Mice","volume":"181","author":"Lucas","year":"2008","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3117","DOI":"10.1002\/eji.200324270","article-title":"Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis","volume":"33","author":"Rodig","year":"2003","journal-title":"Eur. J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.jacc.2019.11.049","article-title":"Global Longitudinal Strain and Cardiac Events in Patients with Immune Checkpoint Inhibitor-Related Myocarditis","volume":"75","author":"Awadalla","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s40425-019-0535-y","article-title":"Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors","volume":"7","author":"Awadalla","year":"2019","journal-title":"J. Immunother. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3653","DOI":"10.1128\/MCB.05020-11","article-title":"1,25-dihydroxyvitamin D(3) ameliorates Th17 autoimmunity via transcriptional modulation of interleu-kin-17A","volume":"31","author":"Joshi","year":"2011","journal-title":"Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.3389\/fimmu.2019.01504","article-title":"Human Memory Th17 Cell Populations Change into Anti-inflammatory Cells with Regulatory Capacity Upon Exposure to Active Vitamin D","volume":"10","author":"Dankers","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1007\/s00432-019-02927-x","article-title":"Immune checkpoint inhibitor therapy and myocar-ditis: A systematic review of reported cases","volume":"145","author":"Kadado","year":"2019","journal-title":"J Cancer Res. Clin. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1093\/cvr\/cvz026","article-title":"Cardio-vascular toxicities associated with immune checkpoint inhibitors","volume":"115","author":"Hu","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/CMR.0000000000000251","article-title":"Myocarditis as an immune-related adverse event with ipili-mumab\/nivolumab combination therapy for metastatic melanoma","volume":"26","author":"Mehta","year":"2016","journal-title":"Melanoma Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1177\/1078155218755868","article-title":"Acute autoimmune myocarditis and hepatitis due to ipilimumab monotherapy for ma-lignant melanoma","volume":"25","author":"Samara","year":"2019","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/CIRCULATIONAHA.118.034497","article-title":"Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syn-dromes in Cardio-Oncology","volume":"140","author":"Bonaca","year":"2019","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1200\/JCO.2017.77.6385","article-title":"National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated with Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline","volume":"36","author":"Brahmer","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.jacc.2019.11.048","article-title":"Echo-Strain to Check Up on Checkpoint Inhibitors","volume":"75","author":"Abraham","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1200\/JCO.18.02464","article-title":"Identification and Management of Immune Checkpoint Inhibitor\u2013Related Myocarditis: Use Troponin Wisely","volume":"37","author":"Spallarossa","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1253\/circj.CJ-10-0017","article-title":"Myocardial Deformation in Acute Myocarditis with Normal Left Ventricular Wall Motion\u2014A Cardiac Magnetic Resonance and 2-Dimensional Strain Echocardiographic Study","volume":"74","author":"Gaeta","year":"2010","journal-title":"Circ. J."},{"key":"ref_39","first-page":"1018","article-title":"Myocardial oedema in acute myocarditis detected by echocardiographic 2D myocardial deformation analysis","volume":"17","author":"Nielsen","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1016\/j.jacc.2018.09.072","article-title":"Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation","volume":"72","author":"Ferreira","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.jacc.2004.11.069","article-title":"Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: Comparison of different approaches","volume":"45","author":"Zagrosek","year":"2005","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrcardio.2014.159","article-title":"Cardiac MRI: A central prognostic tool in myocardial fibrosis","volume":"12","author":"Lima","year":"2015","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1093\/eurheartj\/ehaa051","article-title":"Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis","volume":"41","author":"Zhang","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_44","first-page":"1","article-title":"Myocarditis with checkpoint inhibitor immunotherapy: Case report of late gadolinium enhancement on cardiac magnetic resonance with pathology correlate","volume":"3","author":"Gallegos","year":"2019","journal-title":"Eur. Heart J. Case Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1016\/j.jacc.2011.09.074","article-title":"Update on Myocarditis","volume":"59","author":"Kindermann","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/S0025-6196(12)61286-5","article-title":"Evaluation of Postmortem Endomyocardial Biopsy Specimens From 38 Patients with Lymphocytic Myocarditis: Implications for Role of Sampling Error","volume":"64","author":"Hauck","year":"1989","journal-title":"Mayo Clin. Proc."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3076","DOI":"10.1093\/eurheartj\/ehm456","article-title":"The role of endomyocardial biopsy in the management of cardiovascular disease: A Scientific Statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology Endorsed by the Heart Failure Society of America and the Heart Failure Association of the European Society of Cardiology","volume":"28","author":"Cooper","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"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","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.ahj.2003.09.020","article-title":"Endomyocardial biopsy plays a role in diagnosing patients with unexplained cardiomyopathy","volume":"147","author":"Ardehali","year":"2004","journal-title":"Am. Heart J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1093\/eurheartj\/ehp328","article-title":"Diagnostic synergy of non-invasive cardiovascular magnetic resonance and invasive endomyocardial biopsy in troponin-positive patients without coronary artery disease","volume":"30","author":"Baccouche","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/CJI.0000000000000239","article-title":"Autoimmune Myocarditis Caused by Immune Checkpoint Inhibitors Treated with Antithymocyte Globulin","volume":"41","author":"Jain","year":"2018","journal-title":"J. Immunother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000498985","article-title":"Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature","volume":"12","author":"Agrawal","year":"2019","journal-title":"Case Rep. Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1056\/NEJMc1901677","article-title":"Abatacept for Severe Immune Checkpoint Inhibitor\u2013Associated Myocarditis","volume":"380","author":"Salem","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2375","DOI":"10.1056\/NEJMc1903064","article-title":"Alemtuzumab for Immune-Related Myo-carditis Due to PD-1 Therapy","volume":"380","author":"Esfahani","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1161\/01.CIR.0000077913.60364.D2","article-title":"Anti-TNF Therapy Against Congestive Heart Failure Inves-tigators. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: Results of the anti-TNF Therapy against Conges-tive Heart Failure (ATTACH) trial","volume":"107","author":"Chung","year":"2003","journal-title":"Circulation"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1111\/cas.13433","article-title":"Immune-suppressive effects of interleukin-6 on T-cell-mediated anti-tumor immunity","volume":"109","author":"Tsukamoto","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/nrd.2017.201","article-title":"JAK inhibition as a therapeutic strategy for immune and inflammatory diseases","volume":"16","author":"Schwartz","year":"2017","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Liu, Y., and Jiang, L. (2020). Tofacitinib for treatment in immune-mediated myocarditis: The first reported cases. J. Oncol. Pharm. Pract.","DOI":"10.1177\/1078155220947141"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107211","DOI":"10.1016\/j.carpath.2020.107211","article-title":"Immunomodulatory treatment of immune checkpoint inhibitor-induced myocarditis: Pathway toward preci-sion-based therapy","volume":"47","author":"Balanescu","year":"2020","journal-title":"Cardiovasc. Pathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/82219","article-title":"Statins as a newly recognized type of immunomodulator","volume":"6","author":"Kwak","year":"2000","journal-title":"Nat. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1161\/01.CIR.0000140694.67251.9C","article-title":"Simvastatin induces heme oxygenase-1: A novel mechanism of vessel protection","volume":"110","author":"Lee","year":"2004","journal-title":"Circulation"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1210\/jcem-57-6-1308","article-title":"Specific high-affinity receptors for 1,25-dihydroxyvitamin D3 in human peripheral blood mononuclear cells: Presence in monocytes and induction in T lymphocytes following activation","volume":"57","author":"Bhalla","year":"1983","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1159\/000445577","article-title":"Effects of 1, 25-Dihydroxyvitamin D3 on Experimental Autoimmune Myocarditis in Mice","volume":"38","author":"Hu","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nrc2196","article-title":"Vitamin D signalling pathways in cancer: Potential for anticancer therapeutics","volume":"7","author":"Deeb","year":"2007","journal-title":"Nat. Rev. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e000604","DOI":"10.1136\/jitc-2020-000604","article-title":"Rechallenge patients with immune checkpoint inhibitors following severe immune-related adverse events: Review of the literature and suggested prophylactic strategy","volume":"8","author":"Haanen","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.2217\/imt-2020-0103","article-title":"Outcomes following immunotherapy re-challenge after immune-related adverse event: Sys-tematic review and meta-analysis","volume":"12","author":"Park","year":"2020","journal-title":"Immunotherapy"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/jamaoncol.2020.0726","article-title":"Immune Checkpoint Inhibitor Rechallenge after Immune-Related Adverse Events in Patients with Cancer","volume":"6","author":"Dolladille","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.annonc.2019.10.023","article-title":"Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations","volume":"31","author":"Curigliano","year":"2020","journal-title":"Ann. Oncol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/785\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:06:13Z","timestamp":1760162773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/11\/6\/785"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,22]]},"references-count":69,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["biom11060785"],"URL":"https:\/\/doi.org\/10.3390\/biom11060785","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,22]]}}}