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Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors

The introduction of immune checkpoint inhibitors (ICIs) in oncologic therapies has led to a paradigm shift in cancer treatment. ICIs have increased the overall survival in patients with malignant melanoma, small-cell lung cancer, and many other tumor entities. Despite their clinical benefits, these...

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Autores principales: Duong, Sophie L., Prüss, Harald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294109/
https://www.ncbi.nlm.nih.gov/pubmed/35043373
http://dx.doi.org/10.1007/s13311-022-01184-0
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author Duong, Sophie L.
Prüss, Harald
author_facet Duong, Sophie L.
Prüss, Harald
author_sort Duong, Sophie L.
collection PubMed
description The introduction of immune checkpoint inhibitors (ICIs) in oncologic therapies has led to a paradigm shift in cancer treatment. ICIs have increased the overall survival in patients with malignant melanoma, small-cell lung cancer, and many other tumor entities. Despite their clinical benefits, these novel cancer immunotherapies can induce neurological immune-related adverse events (irAEs). Such immune-mediated complications can manifest within the spectrum of paraneoplastic neurological syndromes (PNSs). PNSs are rare immune-mediated complications of systemic cancers that can involve every aspect of the nervous system. The emergence of PNSs with ICI treatment opens further pathways to study the complex immunopathological interplay of cancer immunity, cross-reactive neurological autoimmune phenomena, and effects of ICIs on the immune system. ICI-induced PNSs comprise a diverse antibody repertoire and phenotypic spectrum with severe and life-threatening disease progression in some cases. Timely diagnosis and urgent interventions are pivotal for a favorable neurologic and oncologic outcome. This review focuses on the pathogenesis of cancer immunotherapy and the disruption of immune tolerance in PNSs and provides an overview of the most pertinent clinical manifestations and principles of diagnostic and therapeutic managements in light of the expected increase in PNSs due to the widespread use of ICIs in clinical practice. This review further discusses potential and evolving concepts of therapeutic monoclonal antibodies for the treatment of PNSs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01184-0.
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spelling pubmed-92941092022-07-20 Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors Duong, Sophie L. Prüss, Harald Neurotherapeutics Review The introduction of immune checkpoint inhibitors (ICIs) in oncologic therapies has led to a paradigm shift in cancer treatment. ICIs have increased the overall survival in patients with malignant melanoma, small-cell lung cancer, and many other tumor entities. Despite their clinical benefits, these novel cancer immunotherapies can induce neurological immune-related adverse events (irAEs). Such immune-mediated complications can manifest within the spectrum of paraneoplastic neurological syndromes (PNSs). PNSs are rare immune-mediated complications of systemic cancers that can involve every aspect of the nervous system. The emergence of PNSs with ICI treatment opens further pathways to study the complex immunopathological interplay of cancer immunity, cross-reactive neurological autoimmune phenomena, and effects of ICIs on the immune system. ICI-induced PNSs comprise a diverse antibody repertoire and phenotypic spectrum with severe and life-threatening disease progression in some cases. Timely diagnosis and urgent interventions are pivotal for a favorable neurologic and oncologic outcome. This review focuses on the pathogenesis of cancer immunotherapy and the disruption of immune tolerance in PNSs and provides an overview of the most pertinent clinical manifestations and principles of diagnostic and therapeutic managements in light of the expected increase in PNSs due to the widespread use of ICIs in clinical practice. This review further discusses potential and evolving concepts of therapeutic monoclonal antibodies for the treatment of PNSs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-022-01184-0. Springer International Publishing 2022-01-18 2022-04 /pmc/articles/PMC9294109/ /pubmed/35043373 http://dx.doi.org/10.1007/s13311-022-01184-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review
Duong, Sophie L.
Prüss, Harald
Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title_full Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title_fullStr Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title_full_unstemmed Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title_short Paraneoplastic Autoimmune Neurological Syndromes and the Role of Immune Checkpoint Inhibitors
title_sort paraneoplastic autoimmune neurological syndromes and the role of immune checkpoint inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9294109/
https://www.ncbi.nlm.nih.gov/pubmed/35043373
http://dx.doi.org/10.1007/s13311-022-01184-0
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