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Immune Related Adverse Events of the Thyroid – A Narrative Review

Immune checkpoints are small molecules present on the cell surface of T-lymphocytes. They maintain self-tolerance and regulate the amplitude and duration of T-cell responses. Antagonism of immune checkpoints with monoclonal antibodies (immune checkpoint inhibitors) is a rapidly evolving field of ant...

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Autores principales: Muir, Christopher A., Tsang, Venessa H. M., Menzies, Alexander M., Clifton-Bligh, Roderick J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178092/
https://www.ncbi.nlm.nih.gov/pubmed/35692394
http://dx.doi.org/10.3389/fendo.2022.886930
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author Muir, Christopher A.
Tsang, Venessa H. M.
Menzies, Alexander M.
Clifton-Bligh, Roderick J.
author_facet Muir, Christopher A.
Tsang, Venessa H. M.
Menzies, Alexander M.
Clifton-Bligh, Roderick J.
author_sort Muir, Christopher A.
collection PubMed
description Immune checkpoints are small molecules present on the cell surface of T-lymphocytes. They maintain self-tolerance and regulate the amplitude and duration of T-cell responses. Antagonism of immune checkpoints with monoclonal antibodies (immune checkpoint inhibitors) is a rapidly evolving field of anti-cancer immunotherapy and has become standard of care in management of many cancer subtypes. Immune checkpoint inhibition is an effective cancer treatment but can precipitate immune related adverse events (irAEs). Thyroid dysfunction is the most common endocrine irAE and can occur in up to 40% of treated patients. Both thyrotoxicosis and hypothyroidism occur. The clinical presentation and demographic associations of thyrotoxicosis compared to hypothyroidism suggest unique entities with different etiologies. Thyroid irAEs, particularly overt thyrotoxicosis, are associated with increased immune toxicity in other organ systems, but also with longer progression-free and overall survival. Polygenic risk scores using susceptibility loci associated with autoimmune thyroiditis predict development of checkpoint inhibitor associated irAEs, suggesting potentially shared mechanisms underpinning their development. Our review will provide an up-to-date summary of knowledge in the field of thyroid irAEs. Major focus will be directed toward pathogenesis (including genetic factors shared with autoimmune thyroid disease), demographic associations, clinical presentation and course, treatment, and the relationship with cancer outcomes.
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spelling pubmed-91780922022-06-10 Immune Related Adverse Events of the Thyroid – A Narrative Review Muir, Christopher A. Tsang, Venessa H. M. Menzies, Alexander M. Clifton-Bligh, Roderick J. Front Endocrinol (Lausanne) Endocrinology Immune checkpoints are small molecules present on the cell surface of T-lymphocytes. They maintain self-tolerance and regulate the amplitude and duration of T-cell responses. Antagonism of immune checkpoints with monoclonal antibodies (immune checkpoint inhibitors) is a rapidly evolving field of anti-cancer immunotherapy and has become standard of care in management of many cancer subtypes. Immune checkpoint inhibition is an effective cancer treatment but can precipitate immune related adverse events (irAEs). Thyroid dysfunction is the most common endocrine irAE and can occur in up to 40% of treated patients. Both thyrotoxicosis and hypothyroidism occur. The clinical presentation and demographic associations of thyrotoxicosis compared to hypothyroidism suggest unique entities with different etiologies. Thyroid irAEs, particularly overt thyrotoxicosis, are associated with increased immune toxicity in other organ systems, but also with longer progression-free and overall survival. Polygenic risk scores using susceptibility loci associated with autoimmune thyroiditis predict development of checkpoint inhibitor associated irAEs, suggesting potentially shared mechanisms underpinning their development. Our review will provide an up-to-date summary of knowledge in the field of thyroid irAEs. Major focus will be directed toward pathogenesis (including genetic factors shared with autoimmune thyroid disease), demographic associations, clinical presentation and course, treatment, and the relationship with cancer outcomes. Frontiers Media S.A. 2022-05-26 /pmc/articles/PMC9178092/ /pubmed/35692394 http://dx.doi.org/10.3389/fendo.2022.886930 Text en Copyright © 2022 Muir, Tsang, Menzies and Clifton-Bligh https://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 Endocrinology
Muir, Christopher A.
Tsang, Venessa H. M.
Menzies, Alexander M.
Clifton-Bligh, Roderick J.
Immune Related Adverse Events of the Thyroid – A Narrative Review
title Immune Related Adverse Events of the Thyroid – A Narrative Review
title_full Immune Related Adverse Events of the Thyroid – A Narrative Review
title_fullStr Immune Related Adverse Events of the Thyroid – A Narrative Review
title_full_unstemmed Immune Related Adverse Events of the Thyroid – A Narrative Review
title_short Immune Related Adverse Events of the Thyroid – A Narrative Review
title_sort immune related adverse events of the thyroid – a narrative review
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9178092/
https://www.ncbi.nlm.nih.gov/pubmed/35692394
http://dx.doi.org/10.3389/fendo.2022.886930
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