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Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect

Targeting B-cell receptor signalling using Bruton tyrosine kinase (BTK) inhibitors (BTKis) has become a highly successful treatment modality for B-cell malignancies, especially for chronic lymphocytic leukaemia. However, long-term administration of BTKis can be complicated by adverse on- and/or off-...

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Autores principales: Wang, Haoran, Guo, Hao, Yang, Jingyi, Liu, Yanyan, Liu, Xingchen, Zhang, Qing, Zhou, Keshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493169/
https://www.ncbi.nlm.nih.gov/pubmed/36138486
http://dx.doi.org/10.1186/s40164-022-00315-9
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author Wang, Haoran
Guo, Hao
Yang, Jingyi
Liu, Yanyan
Liu, Xingchen
Zhang, Qing
Zhou, Keshu
author_facet Wang, Haoran
Guo, Hao
Yang, Jingyi
Liu, Yanyan
Liu, Xingchen
Zhang, Qing
Zhou, Keshu
author_sort Wang, Haoran
collection PubMed
description Targeting B-cell receptor signalling using Bruton tyrosine kinase (BTK) inhibitors (BTKis) has become a highly successful treatment modality for B-cell malignancies, especially for chronic lymphocytic leukaemia. However, long-term administration of BTKis can be complicated by adverse on- and/or off-target effects in particular cell types. BTK is widely expressed in cells of haematopoietic origin, which are pivotal components of the tumour microenvironment. BTKis, thus, show broad immunomodulatory effects on various non-B immune cell subsets by inhibiting specific immune receptors, including T-cell receptor and Toll-like receptors. Furthermore, due to the off-target inhibition of other kinases, such as IL-2-inducible T-cell kinase, epidermal growth factor receptor, and the TEC and SRC family kinases, BTKis have additional distinct effects on T cells, natural killer cells, platelets, cardiomyocytes, and other cell types. Such mechanisms of action might contribute to the exceptionally high clinical efficacy as well as the unique profiles of adverse effects, including infections, bleeding, and atrial fibrillation, observed during BTKi administration. However, the immune defects and related infections caused by BTKis have not received sufficient attention in clinical studies till date. The broad involvement of BTK in immunological pathways provides a rationale to combine BTKis with specific immunotherapies, such as immune checkpoint inhibitor or chimeric antigen receptor-T-cell therapy, for the treatment of relapsed or refractory diseases. This review discusses and summarises the above-mentioned issues as a reference for clinicians and researchers.
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spelling pubmed-94931692022-09-22 Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect Wang, Haoran Guo, Hao Yang, Jingyi Liu, Yanyan Liu, Xingchen Zhang, Qing Zhou, Keshu Exp Hematol Oncol Review Targeting B-cell receptor signalling using Bruton tyrosine kinase (BTK) inhibitors (BTKis) has become a highly successful treatment modality for B-cell malignancies, especially for chronic lymphocytic leukaemia. However, long-term administration of BTKis can be complicated by adverse on- and/or off-target effects in particular cell types. BTK is widely expressed in cells of haematopoietic origin, which are pivotal components of the tumour microenvironment. BTKis, thus, show broad immunomodulatory effects on various non-B immune cell subsets by inhibiting specific immune receptors, including T-cell receptor and Toll-like receptors. Furthermore, due to the off-target inhibition of other kinases, such as IL-2-inducible T-cell kinase, epidermal growth factor receptor, and the TEC and SRC family kinases, BTKis have additional distinct effects on T cells, natural killer cells, platelets, cardiomyocytes, and other cell types. Such mechanisms of action might contribute to the exceptionally high clinical efficacy as well as the unique profiles of adverse effects, including infections, bleeding, and atrial fibrillation, observed during BTKi administration. However, the immune defects and related infections caused by BTKis have not received sufficient attention in clinical studies till date. The broad involvement of BTK in immunological pathways provides a rationale to combine BTKis with specific immunotherapies, such as immune checkpoint inhibitor or chimeric antigen receptor-T-cell therapy, for the treatment of relapsed or refractory diseases. This review discusses and summarises the above-mentioned issues as a reference for clinicians and researchers. BioMed Central 2022-09-22 /pmc/articles/PMC9493169/ /pubmed/36138486 http://dx.doi.org/10.1186/s40164-022-00315-9 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Wang, Haoran
Guo, Hao
Yang, Jingyi
Liu, Yanyan
Liu, Xingchen
Zhang, Qing
Zhou, Keshu
Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title_full Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title_fullStr Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title_full_unstemmed Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title_short Bruton tyrosine kinase inhibitors in B-cell lymphoma: beyond the antitumour effect
title_sort bruton tyrosine kinase inhibitors in b-cell lymphoma: beyond the antitumour effect
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9493169/
https://www.ncbi.nlm.nih.gov/pubmed/36138486
http://dx.doi.org/10.1186/s40164-022-00315-9
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