Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies

被引:20
作者
Xu, Shirley [1 ,2 ]
Sharma, Umesh C. [2 ]
Tuttle, Cheyanna [1 ]
Pokharel, Saraswati [1 ]
机构
[1] Roswell Pk Comprehens Canc Ctr, Div Thorac Pathol & Oncol, Dept Pathol, Buffalo, NY 14203 USA
[2] Univ Buffalo, Dept Med, Jacobs Sch Med & Biomed Sci, Buffalo, NY USA
关键词
cardio-oncology; immunotherapy; PD-1-PDL-1; axis; immune check inhibitor (ICI); immune related adverse effects; ADVERSE EVENTS; B7; FAMILY; PD-1; CANCER; MYOCARDITIS; EXPRESSION; RADIATION; TUMOR; MEMBER; IMMUNOTHERAPY;
D O I
10.3389/fcvm.2021.619650
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Since the approval of the first immune checkpoint inhibitor (ICI) 9 years ago, ICI-therapy have revolutionized cancer treatment. Lately, antibodies blocking the interaction of programmed cell death protein (PD-1) and ligand (PD-L1) are gaining momentum as a cancer treatment, with multiple agents and cancer types being recently approved for treatment by the US Food and Drug Administration (FDA). Unfortunately, immunotherapy often leads to a wide range of immune related adverse events (IRAEs), including several severe cardiac effects and most notably myocarditis. While increased attention has been drawn to these side effects, including publication of multiple clinical observational data, the underlying mechanisms are unknown. In the event of IRAEs, the most widely utilized clinical solution is administration of high dose corticosteroids and in severe cases, discontinuation of these ICIs. This is detrimental as these therapies are often the last line of treatment options for many types of advanced cancer. In this review, we have systematically described the pathophysiology of the PD-1/PD-L1 axis (including a historical perspective) and cardiac effects in pre-clinical models, clinical trials, autoimmune mechanisms, and immunotherapy in combination with other cancer treatments. We have also reviewed the current challenges in the diagnosis of cardiac events and future directions in the field. In conclusion, this review will delve into this expanding field of cancer immunotherapy and the emerging adverse effects that should be quickly detected and prevented.
引用
收藏
页数:7
相关论文
共 64 条
[1]   Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes [J].
Agata, Y ;
Kawasaki, A ;
Nishimura, H ;
Ishida, Y ;
Tsubata, T ;
Yagita, H ;
Honjo, T .
INTERNATIONAL IMMUNOLOGY, 1996, 8 (05) :765-772
[2]  
[Anonymous], 2014, Eli Lilly and Company Prescribing Information for CYRAMZA (Ramucirumab) Injection, for Intravenous UseInitial U.S. Approval
[3]  
[Anonymous], 2014, OPDIVO NIVOLUMAB DRU
[4]  
[Anonymous], 2016, TECENTRIQ ® (Atezolizumab) Injection
[5]  
[Anonymous], 2011, YERVOY IPILIMUMAB DR
[6]   Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis [J].
Awadalla, Magid ;
Mahmood, Syed S. ;
Groarke, John D. ;
Hassan, Malek Z. O. ;
Nohria, Anju ;
Rokicki, Adam ;
Murphy, Sean P. ;
Mercaldo, Nathaniel D. ;
Zhang, Lili ;
Zlotoff, Daniel A. ;
Reynolds, Kerry L. ;
Alvi, Raza M. ;
Banerji, Dahlia ;
Liu, Shiying ;
Heinzerling, Lucie M. ;
Jones-O'Connor, Maeve ;
Bakar, Rula B. ;
Cohen, Justine V. ;
Kirchberger, Michael C. ;
Sullivan, Ryan J. ;
Gupta, Dipti ;
Mulligan, Connor P. ;
Shah, Sachin P. ;
Ganatra, Sarju ;
Rizvi, Muhammad A. ;
Sahni, Gagan ;
Tocchetti, Carlo G. ;
Lawrence, Donald P. ;
Mahmoudi, Michael ;
Devereux, Richard B. ;
Forrestal, Brian J. ;
Mandawat, Anant ;
Lyon, Alexander R. ;
Chen, Carol L. ;
Barac, Ana ;
Hung, Judy ;
Thavendiranathan, Paaladinesh ;
Picard, Michael H. ;
Thuny, Franck ;
Ederhy, Stephane ;
Fradley, Michael G. ;
Neilan, Tomas G. .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2020, 75 (05) :467-478
[7]   Upregulation of Programmed Death-1 and Its Ligand in Cardiac Injury Models: Interaction with GADD153 [J].
Baban, Babak ;
Liu, Jun Yao ;
Qin, Xu ;
Weintraub, Neal L. ;
Mozaffari, Mahmood S. .
PLOS ONE, 2015, 10 (04)
[8]   Heart-Specific Immune Responses in an Animal Model of Autoimmune-Related Myocarditis Mitigated by an Immunoproteasome Inhibitor and Genetic Ablation [J].
Bockstahler, Mariella ;
Fischer, Andrea ;
Goetzke, Carl Christoph ;
Neumaier, Hannah Louise ;
Sauter, Martina ;
Kespohl, Meike ;
Mueller, Anna-Maria ;
Meckes, Christin ;
Salbach, Christian ;
Schenk, Mirjam ;
Heuser, Arnd ;
Landmesser, Ulf ;
Weiner, January ;
Meder, Benjamin ;
Lehmann, Lorenz ;
Kratzer, Adelheid ;
Klingel, Karin ;
Katus, Hugo A. ;
Kaya, Ziya ;
Beling, Antje .
CIRCULATION, 2020, 141 (23) :1885-1902
[9]   Mechanisms regulating PD-L1 expression on tumor and immune cells [J].
Chen, Shuming ;
Crabill, George A. ;
Pritchard, Theresa S. ;
McMiller, Tracee L. ;
Wei, Ping ;
Pardoll, Drew M. ;
Pan, Fan ;
Topalian, Suzanne L. .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7 (01)
[10]  
Dong HD, 1999, NAT MED, V5, P1365