Elsevier

International Journal of Cardiology

Volume 323, 15 January 2021, Pages 179-187
International Journal of Cardiology

Cardiotoxic mechanisms of cancer immunotherapy – A systematic review

https://doi.org/10.1016/j.ijcard.2020.08.033Get rights and content
Under a Creative Commons license
open access

Highlights

  • Active immunotherapies include anti-tumour vaccines and CAR T-cells.

  • Passive agents are antibodies, checkpoint inhibitors, cytokines, T-cell engagers.

  • Myocarditis, heart failure, cardiomyopathy, or pericarditis are cardiac toxicities.

  • Familiarization with these drugs is important to provide adequate patient care.

Abstract

Cancer immunotherapy is a success story of translational medicine that has led to improved survival in patients with different difficult-to-treat types of cancer, such as metastasized melanoma, non-small cell lung cancer or renal cell carcinoma. These novel therapeutic agents exert their antitumor effects by activating the patients' immune system against cancer cells. Immunotherapy can be divided into active agents, such as anti-tumour vaccines or adoptive T-cell transfer, and passive immunotherapies like monoclonal antibodies, checkpoint inhibitors, cytokine therapy, bispecific T-cell engagers.

After initial experimental use, broad clinical application revealed a number of important cardiovascular side effects of immunotherapeutics, which limit treatment options and decrease patients' prognosis and quality of life. With the rising rate of new immunotherapeutics at a hand, the number of patients receiving cancer immunotherapy will constantly increase, resulting in improved long-term survival rates. This review aims to summarize available cancer immunotherapies, their mechanism of action, currently known cardiovascular toxicities and their treatment.

Further optimization of patient care will depend on the combined efforts by oncologists, cardiologists and cardiac surgeons to identify patients at risk and the implementation of interdisciplinary screening and treatment strategies. It is therefore crucial to familiarize heart specialists with novel cancer therapeutics and their potential adverse effects.

Keywords

Cancer immunotherapy
Cardiovascular toxicity
Cardiooncology
Translational medicine

Abbreviations

ADCC
Antibody dependent cellular cytotoxicity
ALCL
Anaplastic large cell lymphoma
ALL
Acute lymphatic leukemia
AMPK
AMP activated kinase
APC
Antigen presenting cells
BcG
Bacillus-Calmette Guerin
BiTE
Bispecific T-cell engager
CAR
Chimeric Antigen Receptor
CEA
Carcinoembryonic Antigen
CD
Cluster of Differentiation
CHF
Chronic heart failure
CLL
Chronic lymphatic leukemia
CMP
Cardiomyopathy
c-Raf
RAF proto-oncogene serine/threonine-protein kinase
CRS
Cytokine Release Syndrome
CTL-4
cytotoxic T-lymphocyte-associated Protein 4
DAMP
Danger associated molecular pattern
DC
Dendritic cell
DLBCL
Diffuse large B-cell lymphoma
ErbB
Erythroblastosis virus oncogene B
EGFR
Epidermal growth factor receptor
FGF
Fibroblast growth factor receptor
Flt-3
Fms-like tyrosine kinase 3
HL
Hodgkin Lymphoma
IFN
Interferon
IL-2
Interleukin 2
IL-6
Interleukin 6
IL-12
Interleukin 12
KRAS
Kirsten rat sarcoma viral oncogen
LV-EF
Left ventricular ejection fraction
LPS
Lipopolysaccharide
mAb
Monoclonal Antibody
MAGE-A3
Melanoma Antigen-A3
MCP-1
Monocyte chemoattractant protein-1
MHC-I
Major Histocompatibility Complex I
MIP-α
Macrophage inflammatory protein alpha
NSTEMI
non ST-elevated myocardial infarction
NK-cells
Natural killer cells
NHL
Non-Hodgkin Lymphoma
NSCLC
Non-Small Cell Lung Cancer
NO
Nitric oxide
PAMP
Pathogen associated molecular pattern
PBMC
Peripheral blood mononuclear cell
PDGF
Platelet derived growth factor
PD-1
Programmed cell death protein 1
PD-L1
Programmed death-ligand 1
PRR
Pattern recognition receptor
ROS
Reactive oxygen species
scFv
single chain variable fragments
SIRS
Systemic inflammatory response syndrome
SLE
Systemic lupus erythematodes
TAA
Tumour associated antigen
TKI
Tyrosine kinase inhibitor
TLR
Toll like receptor
TNF-α
Tumour necrosis factor alpha
VEGF
Vascular endothelial growth factor
VEGFR
Vascular endothelial growth factor receptor

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