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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Published in:	Nature reviews. Endocrinology Vol. 17; no. 7; pp. 389 - 399
Main Authors:	Wright, Jordan J, Powers, Alvin C, Johnson, Douglas B
Format:	Journal Article
Language:	English
Published:	England Nature Publishing Group 01.07.2021
Subjects:	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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Abstract	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.
AbstractList	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.Immune checkpoint inhibitors (ICIs) are now an established cornerstone of cancer therapeutics; however, ICIs are associated with toxicities in various organs, termed immune-related adverse events. This Review highlights current understanding in ICI-induced endocrinopathies, including epidemiology, aetiology, clinical manifestations and approaches to treatment. 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.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. 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.
Author	Wright, Jordan J Powers, Alvin C Johnson, Douglas B
Author_xml	– sequence: 1 givenname: Jordan J orcidid: 0000-0002-2043-0150 surname: Wright fullname: Wright, Jordan J organization: Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA – sequence: 2 givenname: Alvin C surname: Powers fullname: Powers, Alvin C organization: VA Tennessee Valley Healthcare System, Nashville, TN, USA – sequence: 3 givenname: Douglas B orcidid: 0000-0002-6390-773X surname: Johnson fullname: Johnson, Douglas B email: douglas.b.johnson@vumc.org organization: Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, TN, USA. douglas.b.johnson@vumc.org
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/33875857$$D View this record in MEDLINE/PubMed
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PublicationTitle	Nature reviews. Endocrinology
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Snippet	Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target two key signalling pathways related to T cell activation and exhaustion, by binding...
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SubjectTerms	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
Title	Endocrine toxicities of immune checkpoint inhibitors
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