Skip to main content

Advertisement

SpringerLink
Log in

New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity

  • Cardio-oncology (EH Yang, Section Editor)
  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity.

Recent Findings

Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data.

Summary

It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Gong J, Chehrazi-Raffle A, Reddi S, Salgia R. Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J Immunother Cancer. 2018;6(1):8.

    PubMed  PubMed Central  Google Scholar 

  2. Bhullar KS, Lagarón NO, McGowan EM, Parmar I, Jha A, Hubbard BP, et al. Kinase-targeted cancer therapies: progress, challenges and future directions. Mol Cancer. 2018;17(1):48.

    PubMed  PubMed Central  Google Scholar 

  3. Haslam A, Prasad V. Estimation of the percentage of US patients with cancer who are eligible for and respond to checkpoint inhibitor immunotherapy drugs. JAMA Netw Open. 2019;2(5):e192535-e.

    Google Scholar 

  4. Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11(12):852–63.

    CAS  PubMed  Google Scholar 

  5. Jin H-T, Ahmed R, Okazaki T. Role of PD-1 in regulating T-cell immunity. Negative co-receptors and ligands. Springer. 2010:17–37.

  6. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486–99.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.

    CAS  PubMed  Google Scholar 

  8. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ni L, Dong C. New checkpoints in cancer immunotherapy. Immunol Rev. 2017;276(1):52–65.

    CAS  PubMed  Google Scholar 

  10. Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158–68.

    CAS  PubMed  Google Scholar 

  11. Michot J, Bigenwald C, Champiat S, Collins M, Carbonnel F, Postel-Vinay S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016;54:139–48.

    CAS  PubMed  Google Scholar 

  12. Koelzer VH, Rothschild SI, Zihler D, Wicki A, Willi B, Willi N, et al. Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors-an autopsy study. J Immunother Cancer. 2016;4:13. https://doi.org/10.1186/s40425-016-0117-1.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Glass CK, Mitchell RN. Winning the battle, but losing the war: mechanisms and morphology of cancer-therapy-associated cardiovascular toxicity. Cardiovasc Pathol. 2017;30:55–63.

    CAS  PubMed  Google Scholar 

  14. De Martin E, Michot J-M, Papouin B, Champiat S, Mateus C, Lambotte O, et al. Characterization of liver injury induced by cancer immunotherapy using immune checkpoint inhibitors. J Hepatol. 2018;68(6):1181–90.

    PubMed  Google Scholar 

  15. Varricchi G, Marone G, Mercurio V, Galdiero MR, Bonaduce D, Tocchetti CG. Immune checkpoint inhibitors and cardiac toxicity: an emerging issue. Curr Med Chem. 2018;25(11):1327–39.

    CAS  PubMed  Google Scholar 

  16. Wang DY, Salem J-E, Cohen JV, Chandra S, Menzer C, Ye F, et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12):1721–8.

    PubMed  PubMed Central  Google Scholar 

  17. Mir H, Alhussein M, Alrashidi S, Alzayer H, Alshatti A, Valettas N, et al. Cardiac complications associated with checkpoint inhibition: a systematic review of the literature in an important emerging area. Can J Cardiol. 2018;34(8):1059–68.

    PubMed  Google Scholar 

  18. Wang DY, Okoye GD, Neilan TG, Johnson DB, Moslehi JJ. Cardiovascular toxicities associated with cancer immunotherapies. Curr Cardiol Rep. 2017;19(3):21.

    PubMed  Google Scholar 

  19. •• Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, et al. Myocarditis in patients treated with immune checkpoint inhibitors. J Am Coll Cardiol. 2018;71(16):1755–64 An multicenter registry describing clinical features, treatments, and outcomes of 35 patients with ICI-associated myocarditis.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Moslehi JJ, Salem J-E, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391(10124):933.

    PubMed  PubMed Central  Google Scholar 

  21. • Lyon AR, Yousaf N, Battisti NM, Moslehi J, Larkin J. Immune checkpoint inhibitors and cardiovascular toxicity. Lancet Oncol. 2018;19(9):e447–e58 A complete overview on incidence, clinical features and management of immune checkpoint inhibitor induced cardiotoxicity.

    CAS  PubMed  Google Scholar 

  22. Roth ME, Muluneh B, Jensen BC, Madamanchi C, Lee CB. Left ventricular dysfunction after treatment with ipilimumab for metastatic melanoma. Am J Ther. 2016;23(6):e1925–e8.

    PubMed  Google Scholar 

  23. Geisler BP, Raad RA, Esaian D, Sharon E, Schwartz DR. Apical ballooning and cardiomyopathy in a melanoma patient treated with ipilimumab: a case of takotsubo-like syndrome. J Immunother Cancer. 2015;3(1):4.

    PubMed  PubMed Central  Google Scholar 

  24. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti–PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Tawbi HA, Forsyth PA, Algazi A, Hamid O, Hodi FS, Moschos SJ, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. N Engl J Med. 2018;379(8):722–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Salem J-E, Manouchehri A, Moey M, Lebrun-Vignes B, Bastarache L, Pariente A, et al. Cardiovascular toxicities associated with immune checkpoint inhibitors: an observational, retrospective, pharmacovigilance study. Lancet Oncol. 2018;19(12):1579–89.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. •• Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, et al. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–55 A case report of two cases presenting with fulminant myocarditis after nivolumab and ipilimumab combination therapy.

    PubMed  PubMed Central  Google Scholar 

  28. Newman JL, Stone JR. Immune checkpoint inhibition alters the inflammatory cell composition of human coronary artery atherosclerosis. Cardiovasc Pathol. 2019;43:107148.

    CAS  PubMed  Google Scholar 

  29. Nykl R, Fischer O, Vykoupil K, Taborsky M. A unique reason for coronary spasm causing temporary ST elevation myocardial infarction (inferior STEMI)-systemic inflammatory response syndrome after use of pembrolizumab. Arch Med Sci Atheroscler Dis. 2017;2:e100–e2.

    PubMed  PubMed Central  Google Scholar 

  30. Di Giacomo AM, Danielli R, Guidoboni M, Calabrò L, Carlucci D, Miracco C, et al. Therapeutic efficacy of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with metastatic melanoma unresponsive to prior systemic treatments: clinical and immunological evidence from three patient cases. Cancer Immunol Immunother. 2009;58(8):1297–306.

    PubMed  Google Scholar 

  31. Chen D-Y, HuangW-K,Wu VC-C, ChangW-C, Chen J-S, Chuang C-K, et al. Cardiovascular toxicity of immune checkpoint inhibitors in cancer patients: a review when cardiology meets immuno-oncology. J Formos Med Assoc. 2019.

  32. Altan M, Toki MI, Gettinger SN, Carvajal-Hausdorf DE, Zugazagoitia J, Sinard JH, et al. Immune checkpoint inhibitor–associated pericarditis. J Thorac Oncol. 2019;14(6):1102–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Coen M, Rigamonti F, Roth A, Koessler T. Chemotherapy-induced Takotsubo cardiomyopathy, a case report and review of the literature. BMC Cancer. 2017;17(1):394.

    PubMed  PubMed Central  Google Scholar 

  34. Caforio A, Grazzini M, Mann JM, Keeling PJ, Bottazzo GF, McKenna WJ, et al. Identification of alpha-and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Circulation. 1992;85(5):1734–42.

    CAS  PubMed  Google Scholar 

  35. Lauer B, Schannwell M, Kühl U, Strauer B-E, Schultheiss H-P. Antimyosin autoantibodies are associated with deterioration of systolic and diastolic left ventricular function in patients with chronic myocarditis. J Am Coll Cardiol. 2000;35(1):11–8.

    CAS  PubMed  Google Scholar 

  36. Lv H, Havari E, Pinto S, Gottumukkala RV, Cornivelli L, Raddassi K, et al. Impaired thymic tolerance to α-myosin directs autoimmunity to the heart in mice and humans. J Clin Invest. 2011;121(4):1561–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Mueller DL. Mechanisms maintaining peripheral tolerance. Nat Immunol. 2010;11(1):21–7.

    CAS  PubMed  Google Scholar 

  38. Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, et al. Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science. 1995;270(5238):985–8.

    CAS  PubMed  Google Scholar 

  39. Ying H, Yang L, Qiao G, Li Z, Zhang L, Yin F, et al. Cutting edge: CTLA-4–B7 interaction suppresses Th17 cell differentiation. J Immunol. 2010;185(3):1375–8.

    CAS  PubMed  Google Scholar 

  40. Tivol EA, Borriello F, Schweitzer AN, Lynch WP, Bluestone JA, Sharpe AH. 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(5):541–7.

    CAS  PubMed  Google Scholar 

  41. Love VA, Grabie N, Duramad P, Stavrakis G, Sharpe A, Lichtman A. CTLA-4 ablation and Interleukin-12–driven differentiation synergistically augment cardiac pathogenicity of cytotoxic T lymphocytes. Circ Res. 2007;101(3):248–57.

    CAS  PubMed  Google Scholar 

  42. Tarrio ML, Grabie N, Bu D-x, Sharpe AH, Lichtman AH. PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis. J Immunol. 2012;188(10):4876–84.

    CAS  PubMed  Google Scholar 

  43. Lucas JA, Menke J, Rabacal WA, Schoen FJ, Sharpe AH, Kelley VR. Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice. J Immunol. 2008;181(4):2513–21.

    CAS  PubMed  Google Scholar 

  44. Baban B, Liu JY, Qin X, Weintraub NL, Mozaffari MS. Upregulation of programmed death-1 and its ligand in cardiac injury models: interaction with GADD153. PLoS One. 2015;10(4):e0124059.

    PubMed  PubMed Central  Google Scholar 

  45. Grabie N, Gotsman I, DaCosta R, Pang H, Stavrakis G, Butte MJ, et al. Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8+ T-cell mediated injury in the heart. Circulation. 2007;116(18):2062–71.

    CAS  PubMed  Google Scholar 

  46. Agrawal N, Khunger A, Vachhani P, Colvin TA, Hattoum A, Spangenthal E, et al. Cardiac toxicity associated with immune checkpoint inhibitors: case series and review of the literature. Case Rep Oncol. 2019;12(1):260–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Gräni C, Eichhorn C, Bière L, Murthy VL, Agarwal V, Kaneko K, et al. Prognostic value of cardiac magnetic resonance tissue characterization in risk stratifying patients with suspected myocarditis. J Am Coll Cardiol. 2017;70(16):1964–76.

    PubMed  PubMed Central  Google Scholar 

  48. Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZ, Thuny F et al. Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. 2020.

  49. Schnitt S, Stillman I, Owings D, Kishimoto C, Dvorak H, Abelmann W. Myocardial fibrin deposition in experimental viral myocarditis that progresses to dilated cardiomyopathy. Circ Res. 1993;72(4):914–20.

    CAS  PubMed  Google Scholar 

  50. Rinkevich-Shop S, Konen E, Kushnir T, Epstein FH, Landa-Rouben N, Goitein O, et al. Non-invasive assessment of experimental autoimmune myocarditis in rats using a 3 T clinical MRI scanner. Eur Heart J–Cardiovasc Imaging. 2013;14(11):1069–79.

    PubMed  Google Scholar 

  51. Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011;473(7347):317–25.

    CAS  PubMed  Google Scholar 

  52. Kusters PJ, Lutgens E, Seijkens TT. Exploring immune checkpoints as potential therapeutic targets in atherosclerosis. Cardiovasc Res. 2017;114(3):368–77.

    Google Scholar 

  53. Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67–76.

    CAS  PubMed  Google Scholar 

  54. Herbst RS, Baas P, Kim D-W, Felip E, Pérez-Gracia JL, Han J-Y, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016;387(10027):1540–50.

    CAS  PubMed  Google Scholar 

  55. Hu Y-B, Zhang Q, Li H-J, Michot JM, Liu H-B, Zhan P, et al. Evaluation of rare but severe immune related adverse effects in PD-1 and PD-L1 inhibitors in non-small cell lung cancer: a meta-analysis. Transl Lung Cancer Res. 2017;6(Suppl 1):S8–S20.

    PubMed  PubMed Central  Google Scholar 

  56. Korkmaz C, Cansu D, Kaşifoğlu T. Myocardial infarction in young patients (≤ 35 years of age) with systemic lupus erythematosus: a case report and clinical analysis of the literature. Lupus. 2007;16(4):289–97.

    CAS  PubMed  Google Scholar 

  57. Bazaz R, Marriott HM, Francis SE, Dockrell DH. Mechanistic links between acute respiratory tract infections and acute coronary syndromes. J Infect. 2013;66(1):1–17.

    PubMed  Google Scholar 

  58. Navi BB, Reiner AS, Kamel H, Iadecola C, Okin PM, Elkind MS, et al. Risk of arterial thromboembolism in patients with cancer. J Am Coll Cardiol. 2017;70(8):926–38.

    PubMed  PubMed Central  Google Scholar 

  59. Matsumoto T, Sasaki N, Yamashita T, Emoto T, Kasahara K, Mizoguchi T, et al. Overexpression of cytotoxic T-lymphocyte–associated antigen-4 prevents atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2016;36(6):1141–51.

    CAS  PubMed  Google Scholar 

  60. Ma K, Lv S, Liu B, Liu Z, Luo Y, Kong W, et al. CTLA4-IgG ameliorates homocysteine-accelerated atherosclerosis by inhibiting T-cell overactivation in apoE−/− mice. Cardiovasc Res. 2012;97(2):349–59.

    PubMed  Google Scholar 

  61. Bu D-x, Tarrio M, Maganto-Garcia E, Stavrakis G, Tajima G, Lederer J, et al. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol. 2011;31(5):1100–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Gelsomino F, Fiorentino M, Zompatori M, Poerio A, Melotti B, Sperandi F, et al. Programmed death-1 inhibition and atherosclerosis: can nivolumab vanish complicated atheromatous plaques? Ann Oncol. 2017;29(1):284–6.

    Google Scholar 

  63. Lin J, Li M, Wang Z, He S, Ma X, Li D. The role of CD4+CD25+ regulatory T cells in macrophage-derived foam-cell formation. J Lipid Res. 2010;51(5):1208–17. https://doi.org/10.1194/jlr.D000497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Escudier M, Cautela J, Malissen N, Ancedy Y, Orabona M, Pinto J, et al. Clinical features, management, and outcomes of immune checkpoint inhibitor–related cardiotoxicity. Circulation. 2017;136(21):2085–7.

    PubMed  Google Scholar 

  65. Zhou Y-W, Zhu Y-J, Wang M-N, Xie Y, Chen C-Y, Zhang T, et al. Immune checkpoint inhibitor-associated cardiotoxicity: current understanding on its mechanism, diagnosis and management. Front Pharmacol. 2019;10.

  66. Palaskas N, Morgan J, Daigle T, Banchs J, Durand J-B, Hong D, et al. Targeted cancer therapies with pericardial effusions requiring pericardiocentesis focusing on immune checkpoint inhibitors. Am J Cardiol. 2019;123(8):1351–7.

    PubMed  Google Scholar 

  67. Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med. 2005;352(6):539–48.

    CAS  PubMed  Google Scholar 

  68. Tsuchihashi K, Ueshima K, Uchida T, Oh-mura N, Kimura K, Owa M, et al. Transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. J Am Coll Cardiol. 2001;38(1):11–8.

    CAS  PubMed  Google Scholar 

  69. Ederhy S, Cautela J, Ancedy Y, Escudier M, Thuny F, Cohen A. Takotsubo-like syndrome in cancer patients treated with immune checkpoint inhibitors. JACC Cardiovasc Imaging. 2018;2517.

  70. Giza DE, Lopez-Mattei J, Vejpongsa P, Munoz E, Iliescu G, Kitkungvan D, et al. Stress-induced cardiomyopathy in cancer patients. Am J Cardiol. 2017;120(12):2284–8.

    PubMed  Google Scholar 

  71. Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, et al. Current state of knowledge on Takotsubo syndrome: a position statement from the Taskforce on Takotsubo syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2016;18(1):8–27.

    PubMed  Google Scholar 

  72. Lindner AK, Gruenbacher G, Schachtner G, Thurnher M, Pichler R. Rare, but severe: vasculitis and checkpoint inhibitors. Eur Urol Focus. 2019.

  73. Watanabe R, Zhang H, Berry G, Goronzy JJ, Weyand CM. Immune checkpoint dysfunction in large and medium vessel vasculitis. Am J Phys Heart Circ Phys. 2017;312(5):H1052–H9.

    Google Scholar 

  74. Khaddour K, Singh V, Shayuk M. Acral vascular necrosis associated with immune-check point inhibitors: case report with literature review. BMC Cancer. 2019;19(1):449.

    PubMed  PubMed Central  Google Scholar 

  75. Guha A, Al-Kindi S, Jain P, Tashtish N, ElAmm C, Oliveira G. Association between myocarditis and other immune-related adverse events secondary to immune checkpoint inhibitor use. Int J Cancer. 2020. https://doi.org/10.1002/ijc.32960.

  76. Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol Off J Am Soc Clin Oncol. 2018;36(17):1714–68.

    CAS  Google Scholar 

  77. Network NCC. Management of immunotherapy-related toxicities.(Version 1.2019). 2019.

  78. Kwon HJ, Cot TR, Cuffe MS, Kramer JM, Braun MM. Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med. 2003;138(10):807–11.

    PubMed  Google Scholar 

  79. Frigeri M, Meyer P, Banfi C, Giraud R, Hachulla A-L, Spoerl D, et al. Immune checkpoint inhibitor-associated myocarditis: a new challenge for cardiologists. Can J Cardiol. 2018;34(1):92.e1–3.

    Google Scholar 

  80. Tay RY, Blackley E, McLean C, Moore M, Bergin P, Gill S, et al. Successful use of equine anti-thymocyte globulin (ATGAM) for fulminant myocarditis secondary to nivolumab therapy. Br J Cancer. 2017;117(7):921–4.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Salem J-E, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, et al. Abatacept for severe immune checkpoint inhibitor–associated myocarditis. 2019.

Download references

Acknowledgments

None.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Memorial Hospital West, Pembroke Pines, FL, USA

    Arjun Khunger, Ashna Wadhawan & Aditi More

  2. Department of Medicine, Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, UB Office of Graduate Medical Education, 955 Main Street, Suite 7230, Buffalo, NY, 14203-1121, USA

    Lucas Battel & Nikhil Agrawal

  3. Department of Medicine, Rochester General Hospital, Rochester, USA

    Ankita Kapoor

Authors
  1. Arjun Khunger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lucas Battel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashna Wadhawan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Aditi More
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ankita Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nikhil Agrawal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nikhil Agrawal.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest

Human and Animal Rights

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cardio-oncology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khunger, A., Battel, L., Wadhawan, A. et al. New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity. Curr Oncol Rep 22, 65 (2020). https://doi.org/10.1007/s11912-020-00925-8

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11912-020-00925-8

Keywords

Search

Navigation