免疫检查点抑制剂相关心脏毒性的研究进展
Research Progress on Cardiotoxicity Associated with Immune Checkpoint Inhibitors
DOI: 10.12677/ACM.2023.13102348, PDF,   
作者: 赵紫薇, 胡丽婷:西安医学院研究生工作部,陕西 西安;姜 馨*:陕西省人民医院心血管内科,陕西 西安
关键词: 免疫检查点抑制剂心脏毒性心肌炎肿瘤Immune Checkpoint Inhibitors Cardiotoxicity Myocarditis Tumor
摘要: 免疫检查点抑制剂(ICIs)作为一种新型抗肿瘤药物,在治疗多种恶性肿瘤中取得了前所未有的疗效,极大地改善了肿瘤患者的预后。ICIs激活机体免疫细胞的抗肿瘤作用,同时可导致免疫相关毒性反应,其中,心脏毒性反应虽不常见,但死亡率高、预后差,引起了临床医师的高度关注。本文就ICIs心脏毒性的作用机制、临床表现、诊断方法及治疗进行了综述。
Abstract: As a new type of anti-tumor drugs, immune checkpoint inhibitors (ICIs) have achieved unprece-dented efficacy in the treatment of various malignancies, and greatly improved the prognosis of tumor patients. ICIs activate the anti-tumor effects of immune cells in the body, but they can also lead to immune-related toxic reactions. Although cardiotoxicity is not common, they have high mortality and poor prognosis, which has attracted great attention of clinicians. This article reviews the mechanism, clinical manifestations, diagnosis and treatment of ICIs-related cardiotoxicity.
文章引用:赵紫薇, 胡丽婷, 姜馨. 免疫检查点抑制剂相关心脏毒性的研究进展[J]. 临床医学进展, 2023, 13(10): 16772-16778. https://doi.org/10.12677/ACM.2023.13102348

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Sharma, P. and Allison, J.P. (2015) The Future of Immune Checkpoint Therapy. Science, 348, 56-61. [Google Scholar] [CrossRef] [PubMed]
[3] Reck, M., Rodríguez-Abreu, D., Robinson, A.G., et al. (2019) Up-dated Analysis of KEYNOTE-024: Pembrolizumab versus Platinum-Based Chemotherapy for Advanced Non-Small-Cell Lung Cancer with PD-L1 Tumor Proportion Score of 50% or Greater. Journal of Clinical Oncology, 37, 537-546. [Google Scholar] [CrossRef
[4] Durgeau, A., Virk, Y., Corgnac, S., et al. (2018) Recent Advances in Targeting CD8 T-Cell Immunity for More Effective Cancer Immunotherapy. Frontiers in Immunology, 9, Article 14. [Google Scholar] [CrossRef] [PubMed]
[5] Friedman, C.F., Proverbs-Singh, T.A. and Postow, M.A. (2016) Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review. JAMA Oncology, 2, 1346-1353. [Google Scholar] [CrossRef] [PubMed]
[6] Jain, N., Nguyen, H., Chambers, C., et al. (2010) Dual Function of CTLA-4 in Regulatory T cells and Conventional T Cells to Prevent Multiorgan Autoimmunity. Proceedings of the Na-tional Academy of Sciences of the United States of America, 107, 1524-1528. [Google Scholar] [CrossRef] [PubMed]
[7] Seidel, J.A., Otsuka, A. and Kabashima, K. (2018) Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Frontiers in Oncology, 8, Article 86. [Google Scholar] [CrossRef] [PubMed]
[8] Martins, F., Sofiya, L., Sykiotis, G.P., et al. (2019) Adverse Ef-fects of Immune-Checkpoint Inhibitors: Epidemiology, Management and Surveillance. Nature Reviews Clinical Oncology, 16, 563-580. [Google Scholar] [CrossRef] [PubMed]
[9] Mir, H., Alhussein, M., Alrashidi, S., et al. (2018) Cardiac Compli-cations Associated with Checkpoint Inhibition: A Systematic Review of the Literature in an Important Emerging Area. The Canadian Journal of Cardiology, 1059-1068. [Google Scholar] [CrossRef] [PubMed]
[10] Drobni, Z.D., Alvi, R.M., Taron, J., et al. (2020) Association be-tween Immune Checkpoint Inhibitors with Cardiovascular Events and Atherosclerotic Plaque. Circulation, 142, 2299-2311. [Google Scholar] [CrossRef
[11] Khunger, A., Battel, L., Wadhawan, A., et al. (2020) New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity. Current On-cology Reports, 22, Article No. 65. [Google Scholar] [CrossRef] [PubMed]
[12] Love, V.A., Grabie, N., Duramad, P., et al. (2007) CTLA-4 Ab-lation and Interleukin-12 Driven Differentiation Synergistically Augment Cardiac Pathogenicity of Cytotoxic T Lympho-cytes. Circulation Research, 101, 248-257. [Google Scholar] [CrossRef
[13] Wang, J., Okazaki, I.M., Yoshida, T., et al. (2010) PD-1 Deficiency Results in the Development of Fatal Myocarditis in MRL Mice. International Immunology, 22, 443-452. [Google Scholar] [CrossRef] [PubMed]
[14] Okazaki, T., Tanaka, Y., Nishio, R., et al. (2003) Autoantibodies against Cardiac Troponin I Are Responsible for Dilated Cardiomyopathy in PD-1-Deficient Mice. Nature Medicine, 9, 1477-1483. [Google Scholar] [CrossRef] [PubMed]
[15] Johnson, D.B., Balko, J.M., Compton, M.L., et al. (2016) Fulmi-nant Myocarditis with Combination Immune Checkpoint Blockade. The New England Journal of Medicine, 375, 1749-1755. [Google Scholar] [CrossRef
[16] Zou, W., Lu, J. and Hao, Y. (2021) Myocarditis In-duced by Immune Checkpoint Inhibitors: Mechanisms and Therapeutic Prospects. Journal of Inflammation Research, 14, 3077-3088. [Google Scholar] [CrossRef
[17] Mahmood, S.S., Fradley, M.G., Cohen, J.V., et al. (2018) Myocarditis in Patients Treated with Immune Checkpoint Inhibitors. Journal of the American College of Cardiology, 71, 1755-1764. [Google Scholar] [CrossRef] [PubMed]
[18] Escudier, M., Cautela, J., Malissen, N., et al. (2017) Clinical Fea-tures, Management, and Outcomes of Immune Checkpoint Inhibitor-Related Cardiotoxicity. Circulation, 136, 2085-2087. [Google Scholar] [CrossRef
[19] Allenbach, Y., Anquetil, C., Manouchehri, A., et al. (2020) Immune Checkpoint Inhibitor-Induced Myositis, the Earliest and Most Lethal Complication among Rheumatic and Musculoskeletal Toxicities. Autoimmunity Reviews, 19, Article ID: 102586. [Google Scholar] [CrossRef] [PubMed]
[20] Moslehi, J.J., Salem, J.E., Sosman, J.A., et al. (2018) Increased Reporting of Fatal Immune Checkpoint Inhibitor-Associated Myocarditis. Lancet, 391, 933. [Google Scholar] [CrossRef
[21] Lyon, A.R., Yousaf, N., Battisti, N.M.L., et al. (2018) Im-mune Checkpoint Inhibitors and Cardiovascular Toxicity. The Lancet Oncology, 19, e447-e458. [Google Scholar] [CrossRef
[22] Dal'bo, N., Patel, R., Parikh, R., et al. (2020) Cardiotoxicity of Contemporary Anticancer Immunotherapy. Current Treatment Options in Cardiovascular Medicine, 22, Article No. 62. [Google Scholar] [CrossRef] [PubMed]
[23] Ganatra, S. and Neilan, T.G. (2018) Immune Checkpoint In-hibitor-Associated Myocarditis. The Oncologist, 23, 879-886. [Google Scholar] [CrossRef] [PubMed]
[24] Awadalla, M., Mahmood, S.S, Groarke, J.D., et al. (2020) Global Longitudinal Strain and Cardiac Events in Patients with Immune Checkpoint Inhibitor-Related Myocarditis. Jour-nal of the American College of Cardiology, 75, 467-478. [Google Scholar] [CrossRef] [PubMed]
[25] Friedrich, M.G., Sechtem, U., Schulz-Menger, J., et al. (2009) Car-diovascular Magnetic Resonance in Myocarditis: A JACC White Paper. Journal of the American College of Cardiology, 53, 1475-1487. [Google Scholar] [CrossRef] [PubMed]
[26] Zhang, L., Awadalla, M., Mahmood, S.S., et al. (2020) Cardiovas-cular Magnetic Resonance in Immune Checkpoint Inhibitor-Associated Myocarditis. European Heart Journal, 41, 1733-1743. [Google Scholar] [CrossRef] [PubMed]
[27] Nishimura, H., Okazaki, T., Tanaka, Y., et al. (2001) Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice. Science, 291, 319-322. [Google Scholar] [CrossRef] [PubMed]
[28] Berg, D.D., Vaduganathan, M., Nohria, A., et al. (2017) Im-mune-Related Fulminant Myocarditis in a Patient Receiving Ipilimumab Therapy for Relapsed Chronic Myelomonocytic Leukaemia. European Journal of Heart Failure, 19, 682-685. [Google Scholar] [CrossRef] [PubMed]
[29] Zhang, L., Zlo-toff, D.A., Awadalla, M., et al. (2020) Major Adverse Cardiovascular Events and the Timing and Dose of Corticoster-oids in Immune Checkpoint Inhibitor-Associated Myocarditis. Circulation, 141, 2031-2034. [Google Scholar] [CrossRef
[30] Thuny, F., Naidoo, J. and Neilan, T.G. (2022) Cardiovascular Complications of Immune Checkpoint Inhibitors for Cancer. European Heart Journal, 43, 4458-4468. [Google Scholar] [CrossRef] [PubMed]
[31] Pagès, C., Gornet, J.M., Monsel, G., et al. (2013) Ipili-mumab-Induced Acute Severe Colitis Treated by Infliximab. Melanoma Research, 23, 227-230. [Google Scholar] [CrossRef
[32] Heinzerling, L., Ott, P.A., Hodi, F.S., et al. (2016) Cardio-toxicity Associated with CTLA4 and PD1 Blocking Immunotherapy. Journal for Immunotherapy of Cancer, 4, Article 50. [Google Scholar] [CrossRef] [PubMed]
[33] Tay, R.Y., Blackley, E., Mclean, C., et al. (2017) Successful Use of Equine Anti-Thymocyte Globulin (ATGAM) for Fulminant Myocarditis Secondary to Nivolumab Therapy. Brit-ish Journal of Cancer, 117, 921-924. [Google Scholar] [CrossRef] [PubMed]
[34] Agrawal, N., Khunger, A., Vachhani, P., et al. (2019) Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: Case Series and Review of the Literature. Case Reports in Oncology, 12, 260-276. [Google Scholar] [CrossRef] [PubMed]
[35] Hu, J.R., Florido, R., Lipson, E.J., et al. (2019) Cardiovascular Toxicities Associated with Immune Checkpoint Inhibitors. Cardiovascular Research, 115, 854-868. [Google Scholar] [CrossRef] [PubMed]
[36] Esfahani, K., Buhlaiga, N., Thébault, P., et al. (2019) Alemtuzumab for Immune-Related Myocarditis Due to PD-1 Therapy. The New England Journal of Medicine, 380, 2375-2376. [Google Scholar] [CrossRef
[37] Salem, J.E., Allenbach, Y., Vozy, A., et al. (2019) Abatacept for Se-vere Immune Checkpoint Inhibitor-Associated Myocarditis. The New England Journal of Medicine, 380, 2377-2379. [Google Scholar] [CrossRef
[38] Berner, A.M., Sharma, A., Agarwal, S., et al. (2018) Fatal Autoim-mune Myocarditis with Anti-PD-L1 and Tyrosine Kinase Inhibitor Therapy for Renal Cell Cancer. European Journal of Cancer, 101, 287-290. [Google Scholar] [CrossRef] [PubMed]
[39] Guo, X., Wang, H., Zhou, J., et al. (2020) Clinical Manifestation and Management of Immune Checkpoint Inhibitor-Associated Cardiotoxicity. Thoracic Cancer, 11, 475-480. [Google Scholar] [CrossRef] [PubMed]