Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xu, Shirley, Sharma, Umesh C., Tuttle, Cheyanna, Pokharel, Saraswati
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887301/
https://www.ncbi.nlm.nih.gov/pubmed/33614750
http://dx.doi.org/10.3389/fcvm.2021.619650
_version_ 1783651952337354752
author Xu, Shirley
Sharma, Umesh C.
Tuttle, Cheyanna
Pokharel, Saraswati
author_facet Xu, Shirley
Sharma, Umesh C.
Tuttle, Cheyanna
Pokharel, Saraswati
author_sort Xu, Shirley
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7887301
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-78873012021-02-18 Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies Xu, Shirley Sharma, Umesh C. Tuttle, Cheyanna Pokharel, Saraswati Front Cardiovasc Med Cardiovascular Medicine 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. Frontiers Media S.A. 2021-02-03 /pmc/articles/PMC7887301/ /pubmed/33614750 http://dx.doi.org/10.3389/fcvm.2021.619650 Text en Copyright © 2021 Xu, Sharma, Tuttle and Pokharel. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Xu, Shirley
Sharma, Umesh C.
Tuttle, Cheyanna
Pokharel, Saraswati
Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title_full Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title_fullStr Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title_full_unstemmed Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title_short Immune Checkpoint Inhibitors: Cardiotoxicity in Pre-clinical Models and Clinical Studies
title_sort immune checkpoint inhibitors: cardiotoxicity in pre-clinical models and clinical studies
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887301/
https://www.ncbi.nlm.nih.gov/pubmed/33614750
http://dx.doi.org/10.3389/fcvm.2021.619650
work_keys_str_mv AT xushirley immunecheckpointinhibitorscardiotoxicityinpreclinicalmodelsandclinicalstudies
AT sharmaumeshc immunecheckpointinhibitorscardiotoxicityinpreclinicalmodelsandclinicalstudies
AT tuttlecheyanna immunecheckpointinhibitorscardiotoxicityinpreclinicalmodelsandclinicalstudies
AT pokharelsaraswati immunecheckpointinhibitorscardiotoxicityinpreclinicalmodelsandclinicalstudies