Endocrine toxicities of immune checkpoint inhibitors

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and inhibiting cytotoxic T lymphocyte antigen 4 (CTLA4) or PD1 and its ligand PDL1. ICIs, such as nivolumab, pembrolizumab and ipilimumab,...

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Vydáno v:Nature reviews. Endocrinology Ročník 17; číslo 7; s. 389 - 399
Hlavní autoři: Wright, Jordan J, Powers, Alvin C, Johnson, Douglas B
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.07.2021
Témata:
Adrenal glands
Adverse events
Antineoplastic Agents, Immunological - adverse effects
Cancer
Cell activation
CTLA-4 protein
Cytotoxicity
Diabetes mellitus
Drug-Related Side Effects and Adverse Reactions - epidemiology
Drug-Related Side Effects and Adverse Reactions - immunology
Endocrine disorders
Endocrine System Diseases - chemically induced
Endocrine System Diseases - diagnosis
Endocrine System Diseases - epidemiology
Endocrine System Diseases - therapy
Epidemiology
Humans
Hypothyroidism
Immune checkpoint inhibitors
Immune Checkpoint Inhibitors - adverse effects
Immune System - drug effects
Immune System - physiology
Immunotherapy
Immunotherapy - adverse effects
Lymphocytes T
Monoclonal antibodies
Morbidity
Neoplasms - drug therapy
Neoplasms - epidemiology
Neoplasms - immunology
Pancreas
PD-1 protein
Pembrolizumab
Pituitary
Signal transduction
Thyroid
Thyrotoxicosis
ISSN:1759-5029, 1759-5037, 1759-5037
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Popis
Shrnutí:Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding to and inhibiting cytotoxic T lymphocyte antigen 4 (CTLA4) or PD1 and its ligand PDL1. ICIs, such as nivolumab, pembrolizumab and ipilimumab, are approved for the treatment of numerous and diverse cancer types, in various combination regimens, and are now an established cornerstone of cancer therapeutics. Toxicities induced by ICIs are autoimmune in nature and are referred to as immune-related adverse events (irAEs); these events can affect any organ system in an unpredictable fashion. Importantly, irAEs can manifest as endocrinopathies involving the thyroid (hypothyroidism or thyrotoxicosis), pituitary (hypophysitis), adrenal glands (adrenal insufficiency) and pancreas (diabetes mellitus). These events are a frequent source of acute and persistent morbidity in patients treated with ICIs and can even be fatal. Over the past few years, there has been a growing understanding of the underlying pathogenesis of irAEs that has led to the development of more effective management strategies. Herein, we review the current understanding of the pathobiology, clinical manifestations and treatment approaches to endocrine toxicities arising from ICIs.
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ISSN:1759-5029
1759-5037
1759-5037
DOI:10.1038/s41574-021-00484-3