{"id":66,"date":"2021-11-10T11:37:18","date_gmt":"2021-11-10T03:37:18","guid":{"rendered":"http:\/\/lw.gdpmaa.com\/?p=66"},"modified":"2021-11-10T11:37:18","modified_gmt":"2021-11-10T03:37:18","slug":"%e5%85%8d%e7%96%ab%e6%a3%80%e6%9f%a5%e7%82%b9%e6%8a%91%e5%88%b6%e5%89%82%e7%9b%b8%e5%85%b3%e6%80%a7%e5%bf%83%e8%82%8c%e7%82%8e%e7%9a%84%e7%a0%94%e7%a9%b6%e8%bf%9b%e5%b1%95","status":"publish","type":"post","link":"http:\/\/lw.gdpmaa.com\/?p=66","title":{"rendered":"\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\u76f8\u5173\u6027\u5fc3\u808c\u708e\u7684\u7814\u7a76\u8fdb\u5c55"},"content":{"rendered":"\n<p>                                                    <strong>\u738b\u674e\u5f3a<sup><strong><sup>1\uff0c2#<\/sup><\/strong><\/sup><\/strong><strong>\uff0c\u8c22\u6653\u9e3f<sup><strong><sup>1<\/sup><\/strong><\/sup><\/strong><strong>\uff0c\u5468\u627f\u5fd7<sup><strong><sup>1*<\/sup><\/strong><\/sup><\/strong><\/p>\n\n\n\n<p>1.\u547c\u5438\u4e0e\u5371\u91cd\u75c7\u533b\u5b66\u90e8\uff0c\u5e7f\u5dde\u533b\u79d1\u5927\u5b66\u9644\u5c5e\u7b2c\u4e00\u533b\u9662\uff0c\u5e7f\u5dde\u533b\u79d1\u5927\u5b66\uff0c\u5e7f\u5dde\u5e02\uff0c\u5e7f\u4e1c\u7701<\/p>\n\n\n\n<p>2.\u751f\u547d\u79d1\u5b66\u5b66\u9662\uff0c\u6cb3\u5357\u5927\u5b66\uff0c\u5f00\u5c01\u5e02\uff0c\u6cb3\u5357\u7701<\/p>\n\n\n\n<p>#\u7b2c\u4e00\u4f5c\u8005:\u738b\u674e\u5f3a\uff0cE-mail:Wang_37@live.cn,tel:13030191582<\/p>\n\n\n\n<p>*\u901a\u8baf\u4f5c\u8005:\u5468\u627f\u5fd7\uff1bE-mail:doctorzcz@163.com,tel:13560351186<\/p>\n\n\n\n<p><strong>\u6458\u8981<\/strong>&nbsp;\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242(ICIs)\u73b0\u5df2\u6210\u4e3a\u591a\u80bf\u7624\u7684\u6807\u51c6\u6cbb\u7597\uff0cICIs\u5728\u6fc0\u6d3bT\u7ec6\u80de\u53d1\u6325\u6297\u80bf\u7624\u4f5c\u7528\uff0c\u4e5f\u5bfc\u81f4\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\uff08irAEs\uff09\uff0cICIs\u76f8\u5173\u5fc3\u808c\u708e\uff08ICIs-\u5fc3\u808c\u708e\uff09\u662f\u5176\u4e2d\u4e00\u79cd\u53d1\u751f\u7387\u4f4e\u4f46\u75c5\u6b7b\u7387\u9ad8\u7684irAE\u3002\u672c\u6587\u56de\u987e\u8fd1\u671fICIs\u7684\u7814\u7a76\u6210\u679c\uff0c\u603b\u7ed3ICIs-\u5fc3\u808c\u708e\u6d41\u884c\u75c5\u5b66\u3001\u53d1\u75c5\u673a\u5236\u3001\u4e34\u5e8a\u7279\u70b9\u548c\u8bca\u65ad\uff0c\u4ee5\u63d0\u9ad8\u4e34\u5e8a\u533b\u751fICIs-\u5fc3\u808c\u708e\u7684\u8ba4\u8bc6\u3002<strong><\/strong><\/p>\n\n\n\n<p><strong>\u5173\u952e\u8bcd<\/strong>&nbsp;\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242\uff1b\u5fc3\u808c\u708e\uff1b\u7a0b\u5e8f\u6027\u6b7b\u4ea1\u53d7\u4f53-1\uff1b\u7ec6\u80de\u6bd2T\u6dcb\u5df4\u7ec6\u80de\u76f8\u5173\u6297\u539f-4\u3002<\/p>\n\n\n\n<p>\u8fd1\u5e74\u6765\uff0c\u514d\u75ab\u68c0\u67e5\u70b9\u6291\u5236\u5242(ICIs)\u5728\u591a\u79cd\u80bf\u7624\u4e2d\u53d6\u5f97\u4e86\u4ee4\u4eba\u77a9\u76ee\u7684\u7597\u6548\u5e76\u6539\u53d8\u4e86\u4f20\u7edf\u80bf\u7624\u7684\u6cbb\u7597\u7b56\u7565\u3002\u514d\u75ab\u6cbb\u7597\u8fc7\u7a0b\u4e2d\u53ef\u51fa\u73b0\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6 (irAEs)\uff0c\u751a\u81f3\u53d1\u5c55\u4e3a\u81f4\u547d\u6027\u4e0d\u826f\u4e8b\u4ef6(FAEs)\u3002ICIs\u76f8\u5173\u6027\u5fc3\u808c\u708e(ICIs-\u5fc3\u808c\u708e)\u662f\u4e00\u79cd\u53d1\u751f\u7387\u4f4e\u4f46\u81f4\u6b7b\u7387\u9ad8\u7684irAE\u3002\u672c\u6587\u5c31ICIs-\u5fc3\u808c\u708e\u7684\u6d41\u884c\u75c5\u5b66\u3001\u53d1\u75c5\u673a\u5236\u3001\u4e34\u5e8a\u7279\u70b9\u548c\u8bca\u65ad\u7b49\u591a\u65b9\u9762\u7684\u7814\u7a76\u8fdb\u5c55\u7efc\u8ff0\u5982\u4e0b\u3002<\/p>\n\n\n\n<ol type=\"1\"><li><strong>ICIs-\u5fc3\u808c\u708e\u6d41\u884c\u75c5\u5b66<\/strong><strong><\/strong><\/li><\/ol>\n\n\n\n<p>ICIs-\u5fc3\u808c\u708e\u662f\u4e00\u79cd\u6b7b\u4ea1\u7387\u6781\u9ad8\u7684irAEs\uff0c\u65e2\u5f80ICIs\u7684\u4e34\u5e8a\u8bd5\u9a8c\u4e2d\u5fc3\u810f\u6bd2\u6027\u7684\u62a5\u544a\u5f88\u5c11,\u5176\u771f\u5b9e\u53d1\u75c5\u7387\u672a\u77e5(1)\u3002<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Wang DY[Author]&amp;cauthor=true&amp;cauthor_uid=30242316\">Wang<\/a>\u7b49\u8fdb\u884c\u4e86\u4e00\u9879meta\u5206\u6790\u7eb3\u516519217\u540d\u60a3\u8005\uff0c\u5171122\u540d\u60a3\u8005\u51fa\u73b0\u81f4\u547d\u6027\u4e0d\u826f\u4e8b\u4ef6\uff0c\u5176\u4e2d9\u540d\u53d1\u751f\u5fc3\u810f\u4e8b\u4ef6(2)\u3002\u771f\u5b9e\u4e16\u754c\u4e2d\uff0cMahmood\u7b49\u56de\u987e\u4e868\u4e2a\u4e2d\u5fc3\u63a5\u53d7ICIs\u6cbb\u7597\u7684\u60a3\u8005\uff0cICIs-\u5fc3\u808c\u708e\u7684\u53d1\u751f\u7387\u4e3a1.14%(3)\u3002\u5728\u836f\u7269\u7814\u7a76\u5b89\u5168\u6027\u6570\u636e\u5e93VigiBase\u5206\u6790\u4e2d\uff0c<a href=\"https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/?term=Salem JE[Author]&amp;cauthor=true&amp;cauthor_uid=30442497\">Salem<\/a>\u7b49\u7eb3\u5165\u4e8631321\u4f8birAEs\u75c5\u4f8b\uff0c\u5fc3\u808c\u708e\u5360\u6bd4\u4e3a0.39%\uff0c\u800cWang\u7b5b\u67e5\u51fa613\u4e2a\u81f4\u547d\u7684irAEs\uff0c\u5176\u4e2d\u5fc3\u808c\u708e\u53605.5%(2, 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40)\u3002<\/p>\n\n\n\n<p>ECG\u56e0\u5176\u4fbf\u5229\u6027\u5728\u8bc6\u522b\u548c\u8bca\u65ad\u53ef\u7591ICIs-\u5fc3\u808c\u708e\u4e0a\u53d1\u6325\u7740\u91cd\u8981\u4f5c\u7528\uff0cICIs\u76f8\u5173\u6bd2\u6027\u4e2d40-89%\u53ef\u51fa\u73b0\u5fc3\u7535\u56fe\u7684\u5f02\u5e38\u53d8\u5316\uff0c\u4f46\u8fd9\u4e9b\u53d8\u5316\u5f80\u5f80\u662f\u975e\u7279\u5f02\u6027\u7684\uff1b\u9700\u8981\u6ce8\u610f\u7684\u662f\uff0c\u5373\u4f7fECG\u62a5\u544a\u6b63\u5e38\uff0c\u4e5f\u4e0d\u80fd\u6392\u9664\u5fc3\u808c\u708e(3, 6, 24, 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42)\u3002<\/p>\n\n\n\n<p>\u76f8\u6bd4\u4e8e\u8d85\u58f0\u5fc3\u52a8\u56fe\uff0ccMRI\u662f\u4e00\u79cd\u66f4\u4f18\u7684\u65e0\u521b\u6027\u8bca\u65ad\u8bca\u624b\u6bb5\uff0c\u5728\u5fc3\u808c\u708e\u7684\u65e9\u671f\u68c0\u6d4b\u548c\u8fde\u7eed\u76d1\u6d4b\u4e2d\u8d77\u7740\u5173\u952e\u4f5c\u7528\u3002cMRI\u53ef\u663e\u793a\u5fc3\u808c\u708e\u7ec4\u7ec7\u7279\u5f81\uff0c\u5982\u663e\u793a\u5fc3\u808c\u6c34\u80bf\u548c\u665a\u671f\u9486\u589e\u5f3a (LGE)\uff0c\u4e3a\u65e9\u671f\u8840\u6d41\u52a8\u529b\u5b66\u7a33\u5b9a\u7684\u5fc3\u808c\u708e\u60a3\u8005\u63d0\u4f9b\u4e86\u5fc3\u808c\u708e\u75c7\u548c\u7ea4\u7ef4\u5316\u7684\u8bca\u65ad\u4f9d\u636e(43, 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\/CD8+ T\u6dcb\u5df4\u7ec6\u80de\u548cCD68+\u5de8\u566c\u7ec6\u80de\u4e3a\u4e3b\uff0c\u8fd8\u6709\u4e00\u4e9bCD4+T\u7ec6\u80de\uff0c\u55dc\u9178\u6027\u7c92\u7ec6\u80de\u3001\u5de8\u7ec6\u80de\u3001B\u7ec6\u80de\u6d78\u6da6\u4ee5\u53ca\u8089\u82bd\u5c11\u89c1\u80bf\uff0c\u6297\u4f53\u6c89\u79ef\u660e\u663e\u7f3a\u4e4f(5, 38, 46-49)\u3002\u5c3d\u7ba1EMB\u5728\u8bca\u65ad\u5fc3\u808c\u708e\u65b9\u9762\u7279\u5f02\u5ea6\u5f88\u9ad8\uff0c\u4f46\u53d7\u9650\u4e8e\u6280\u672f\u6027\u539f\u56e0\uff0c\u5982\u53d6\u6750\u90e8\u4f4d\u4e0d\u51c6\u6216\u6591\u7247\u72b6\u6216\u5c40\u7076\u6027\u5fc3\u808c\u708e\u53ef\u80fd\u5bfc\u81f4\u5fc3\u808c\u708e\u7684\u6f0f\u8bca\uff0c\u5176\u654f\u611f\u5ea6\u8f83\u5dee(50)\u3002\u6b64\u5916\uff0cEMB\u6709\u5fc3\u810f\u7a7f\u5b54\u3001\u5fc3\u5305\u586b\u585e\u3001\u5fc3\u5f8b\u5931\u5e38\u7b49\u4e25\u91cd\u5e76\u53d1\u75c7\u7684\u98ce\u9669\uff0c\u56e0\u6b64\u5fc5\u987b\u6743\u8861\u98ce\u9669\u4e0e\u83b7\u76ca\u624d\u80fd\u8fdb\u884c\u3002<\/p>\n\n\n\n<ul><li><strong>\u5c0f\u7ed3<\/strong><\/li><\/ul>\n\n\n\n<p>ICIs-\u5fc3\u808c\u708e\u662f\u4e00\u79cd\u5c11\u89c1\u7684irAE\uff0c\u5177\u6709\u53d1\u75c5\u65f6\u95f4\u65e9\u3001\u6613\u51fa\u73b0\u66b4\u53d1\u6027\u8fdb\u5c55\u3001\u6b7b\u4ea1\u7387\u9ad8\u7684\u7279\u70b9\uff0c\u5176\u53d1\u75c5\u673a\u5236\u5c1a\u672a\u5b8c\u5168\u9610\u660e\u3002ICIs-\u5fc3\u808c\u708e\u4e34\u5e8a\u8868\u73b0\u7f3a\u4e4f\u7279\u5f02\u6027\uff0c\u5728\u6000\u7591\u5fc3\u808c\u708e\u65f6\u5fc5\u987b\u5c3d\u5feb\u8fdb\u5165\u8bca\u65ad\u6d41\u7a0b\uff0c\u8003\u8651\u5404\u79cd\u68c0\u6d4b\u65b9\u5f0f\u90fd\u5b58\u5728\u7279\u5f02\u6027\u6216\u654f\u611f\u6027\u5dee\u7684\u95ee\u9898\uff0c\u5e94\u8054\u5408\u591a\u79cd\u8bca\u65ad\u65b9\u5f0f\u8fdb\u884c\u7efc\u5408\u8bc4\u4f30\u3002<\/p>\n\n\n\n<p><strong>References:<\/strong><\/p>\n\n\n\n<p>&nbsp;1. <a><\/a>Sury K, Perazella MA, Shirali AC. Cardiorenal complications of immune checkpoint inhibitors. NAT REV NEPHROL 2018;14:571-588<\/p>\n\n\n\n<p>&nbsp;2. <a><\/a>Wang DY, Salem JE, Cohen JV, et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA ONCOL 2018;4:1721-1728<\/p>\n\n\n\n<p>&nbsp;3. <a><\/a>Mahmood SS, Fradley MG, Cohen JV, et al. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J AM COLL CARDIOL 2018;71:1755-1764<\/p>\n\n\n\n<p>&nbsp;4. <a><\/a>Salem JE, Manouchehri A, Moey M, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. LANCET ONCOL 2018;19:1579-1589<\/p>\n\n\n\n<p>&nbsp;5. <a><\/a>Johnson DB, Balko JM, Compton ML, et al. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med 2016;375:1749-1755<\/p>\n\n\n\n<p>&nbsp;6. <a><\/a>Neilan TG, Rothenberg ML, Amiri-Kordestani L, et al. Myocarditis Associated with Immune Checkpoint Inhibitors: An Expert Consensus on &nbsp;Data Gaps and a Call to Action. ONCOLOGIST 2018;23:874-878<\/p>\n\n\n\n<p>&nbsp;7. <a><\/a>Escudier M, Cautela J, Malissen N, et al. Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity. CIRCULATION 2017;136:2085-2087<\/p>\n\n\n\n<p>&nbsp;8. <a><\/a>Noseda R, Ruinelli L, Gaag L, et al. Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study. Cancers (Basel) 2020;12<\/p>\n\n\n\n<p>&nbsp;9. <a><\/a>Drobni ZD, Zafar A, Zubiri L, et al. Decreased Absolute Lymphocyte Count and Increased Neutrophil\/Lymphocyte Ratio With Immune Checkpoint Inhibitor-Associated Myocarditis. J AM HEART ASSOC 2020;9:e18306<\/p>\n\n\n\n<p>10. <a><\/a>Waterhouse P, Penninger JM, Timms E, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. SCIENCE 1995;270:985-988<\/p>\n\n\n\n<p>11. <a><\/a>Ying H, Yang L, Qiao G, et al. Cutting edge: CTLA-4&#8211;B7 interaction suppresses Th17 cell differentiation. J IMMUNOL 2010;185:1375-1378<\/p>\n\n\n\n<p>12. <a><\/a>Tivol EA, Borriello F, Schweitzer AN, et al. Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4. IMMUNITY 1995;3:541-547<\/p>\n\n\n\n<p>13. <a><\/a>Love VA, Grabie N, Duramad P, et al. CTLA-4 ablation and interleukin-12 driven differentiation synergistically augment cardiac pathogenicity of cytotoxic T lymphocytes. CIRC RES 2007;101:248-257<\/p>\n\n\n\n<p>14. <a><\/a>Lucas JA, Menke J, Rabacal WA, et al. Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice. J IMMUNOL 2008;181:2513-2521<\/p>\n\n\n\n<p>15. <a><\/a>Tarrio ML, Grabie N, Bu DX, et al. PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J IMMUNOL 2012;188:4876-4884<\/p>\n\n\n\n<p>16. <a><\/a>Baban B, Liu JY, Qin X, et al. Upregulation of Programmed Death-1 and Its Ligand in Cardiac Injury Models: Interaction with GADD153. PLOS ONE 2015;10:e124059<\/p>\n\n\n\n<p>17. <a><\/a>Grabie N, Gotsman I, DaCosta R, et al. Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart. CIRCULATION 2007;116:2062-2071<\/p>\n\n\n\n<p>18. <a><\/a>Wang J, Okazaki IM, Yoshida T, et al. PD-1 deficiency results in the development of fatal myocarditis in MRL mice. INT IMMUNOL 2010;22:443-452<\/p>\n\n\n\n<p>19. <a><\/a>Nishimura H, Okazaki T, Tanaka Y, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. SCIENCE 2001;291:319-322<\/p>\n\n\n\n<p>20. <a><\/a>Caforio AL, Grazzini M, Mann JM, et al. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. CIRCULATION 1992;85:1734-1742<\/p>\n\n\n\n<p>21. <a><\/a>Lauer B, Schannwell M, Kuhl U, et al. Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis. J AM COLL CARDIOL 2000;35:11-18<\/p>\n\n\n\n<p>22. <a><\/a>Lv H, Havari E, Pinto S, et al. Impaired thymic tolerance to alpha-myosin directs autoimmunity to the heart in mice and humans. J CLIN INVEST 2011;121:1561-1573<\/p>\n\n\n\n<p>23. <a><\/a>Varricchi G, Galdiero MR, Marone G, et al. Cardiotoxicity of immune checkpoint inhibitors. ESMO Open 2017;2:e247<\/p>\n\n\n\n<p>24. <a><\/a>Tocchetti CG, Galdiero MR, Varricchi G. Cardiac Toxicity in Patients Treated With Immune Checkpoint Inhibitors: It Is Now Time for Cardio-Immuno-Oncology. J AM COLL CARDIOL 2018;71:1765-1767<\/p>\n\n\n\n<p>25. <a><\/a>Tsuruda T, Yoshikawa N, Kai M, et al. The Cytokine Expression in Patients with Cardiac Complication after Immune Checkpoint Inhibitor Therapy. Intern Med 2021;60:423-429<\/p>\n\n\n\n<p>26. <a><\/a>Kumar P, Saini S, Prabhakar BS. Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis. SEMIN CANCER BIOL 2020;64:29-35<\/p>\n\n\n\n<p>27. <a><\/a>Simpson TR, Li F, Montalvo-Ortiz W, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J EXP MED 2013;210:1695-1710<\/p>\n\n\n\n<p>28. <a><\/a>Selby MJ, Engelhardt JJ, Quigley M, et al. Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. CANCER IMMUNOL RES 2013;1:32-42<\/p>\n\n\n\n<p>29. <a><\/a>Romano E, Kusio-Kobialka M, Foukas PG, et al. Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by &nbsp;nonclassical monocytes in melanoma patients. Proc Natl Acad Sci U S A 2015;112:6140-6145<\/p>\n\n\n\n<p>30. <a><\/a>Liakou CI, Kamat A, Tang DN, et al. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio &nbsp;of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A 2008;105:14987-14992<\/p>\n\n\n\n<p>31. <a><\/a>Kumar P, Saini S, Prabhakar BS. Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis. SEMIN CANCER BIOL 2020;64:29-35<\/p>\n\n\n\n<p>32. <a><\/a>Alissafi T, Hatzioannou A, Legaki AI, et al. Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells. J AUTOIMMUN 2019;104:102310<\/p>\n\n\n\n<p>33. <a><\/a>Laubli H, Balmelli C, Bossard M, et al. Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma. J IMMUNOTHER CANCER 2015;3:11<\/p>\n\n\n\n<p>34. <a><\/a>Hu JR, Florido R, Lipson EJ, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors. CARDIOVASC RES 2019;115:854-868<\/p>\n\n\n\n<p>35. <a><\/a>Escudier M, Cautela J, Malissen N, et al. Clinical Features, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity. CIRCULATION 2017;136:2085-2087<\/p>\n\n\n\n<p>36. <a><\/a>Behling J, Kaes J, Munzel T, et al. New-onset third-degree atrioventricular block because of autoimmune-induced myositis under treatment with anti-programmed cell death-1 (nivolumab) for metastatic melanoma. MELANOMA RES 2017;27:155-158<\/p>\n\n\n\n<p>37. <a><\/a>Lyon AR, Yousaf N, Battisti N, et al. Immune checkpoint inhibitors and cardiovascular toxicity. LANCET ONCOL 2018;19:e447-e458<\/p>\n\n\n\n<p>38. <a><\/a>Ji C, Roy MD, Golas J, et al. Myocarditis in Cynomolgus Monkeys Following Treatment with Immune Checkpoint Inhibitors. CLIN CANCER RES 2019;25:4735-4748<\/p>\n\n\n\n<p>39. <a><\/a>Chen Q, Huang DS, Zhang LW, et al. Fatal myocarditis and rhabdomyolysis induced by nivolumab during the treatment of type B3 thymoma. Clin Toxicol (Phila) 2018;56:667-671<\/p>\n\n\n\n<p>40. <a><\/a>Agrawal N, Khunger A, Vachhani P, et al. Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature. Case Rep Oncol 2019;12:260-276<\/p>\n\n\n\n<p>41. <a><\/a>Tajiri K, Aonuma K, Sekine I. Immune checkpoint inhibitor-related myocarditis. JPN J CLIN ONCOL 2018;48:7-12<\/p>\n\n\n\n<p>42. <a><\/a>Conforti F, Pala L, Bagnardi V, et al. Cancer immunotherapy efficacy and patients&#8217; sex: a systematic review and meta-analysis. LANCET ONCOL 2018;19:737-746<\/p>\n\n\n\n<p>43. <a><\/a>Friedrich MG, Sechtem U, Schulz-Menger J, et al. Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. J AM COLL CARDIOL 2009;53:1475-1487<\/p>\n\n\n\n<p>44. <a><\/a>Aquaro GD, Perfetti M, Camastra G, et al. Cardiac MR With Late Gadolinium Enhancement in Acute Myocarditis With Preserved Systolic Function: ITAMY Study. J AM COLL CARDIOL 2017;70:1977-1987<\/p>\n\n\n\n<p>45. <a><\/a>Arponen O, Skytta T. Immune checkpoint inhibitor-induced myocarditis not visible with cardiac magnetic resonance imaging but detected with PET-CT: a case report. ACTA ONCOL 2020;59:490-492<\/p>\n\n\n\n<p>46. <a><\/a>Ibraheim H, Perucha E, Powell N. Pathology of immune-mediated tissue lesions following treatment with immune checkpoint inhibitors. Rheumatology (Oxford) 2019;58:i17-i28<\/p>\n\n\n\n<p>47. <a><\/a>Sobol I, Chen CL, Mahmood SS, et al. Histopathologic Characterization of Myocarditis Associated With Immune Checkpoint Inhibitor Therapy. ARCH PATHOL LAB MED 2020;144:1392-1396<\/p>\n\n\n\n<p>48. <a><\/a>Zhang L, Awadalla M, Mahmood SS, et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. EUR HEART J 2020;41:1733-1743<\/p>\n\n\n\n<p>49. <a><\/a>Reuben A, Petaccia DMM, McQuade J, et al. Comparative immunologic characterization of autoimmune giant cell myocarditis with ipilimumab. ONCOIMMUNOLOGY 2017;6:e1361097<\/p>\n\n\n\n<p>50. <a><\/a>Asnani A. Cardiotoxicity of Immunotherapy: Incidence, Diagnosis, and Management. 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