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The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells
The PI3Kδ-inhibitor Idelalisib is approved for the treatment of Non-Hodgkin lymphoma. However, its use has been decreased within the last years due to deleterious infections such as cytomegalovirus and pneumocystis jirovecii. Here, we have investigated the effect of Idelalisib on human monocyte-deri...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571156/ https://www.ncbi.nlm.nih.gov/pubmed/34173009 http://dx.doi.org/10.1007/s00262-021-02988-3 |
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author | Braun, Christiane Schlaweck, Sebastian Daecke, Solveig Nora Brossart, Peter Heine, Annkristin |
author_facet | Braun, Christiane Schlaweck, Sebastian Daecke, Solveig Nora Brossart, Peter Heine, Annkristin |
author_sort | Braun, Christiane |
collection | PubMed |
description | The PI3Kδ-inhibitor Idelalisib is approved for the treatment of Non-Hodgkin lymphoma. However, its use has been decreased within the last years due to deleterious infections such as cytomegalovirus and pneumocystis jirovecii. Here, we have investigated the effect of Idelalisib on human monocyte-derived dendritic cells (DCs) as important players in the induction of immune responses. We found that Idelalisib-treated DCs displayed impaired T cell stimulatory function. PI3Kδ inhibition during differentiation resulted in decreased Interleukin-12, Interleukin-13 and TNFα production by DCs after lipopolysaccharide stimulation. Moreover, DCs showed decreased expression of the activation marker CD83 after Idelalisib treatment. Further, in line with this was the failure of Idelalisib-treated DCs to properly induce allogeneic T cells in a dose-dependent manner. Finally, activation of the NFκB pathway was also ablated in Idelalisib-treated DCs. Our results implicate that severe infectious complications may not only result from direct PI3Kδ-inhibition in T cells, but also from impaired DC function in Idelalisib-treated patients. Here, we provide new insight into the pathogenesis of Idelalisib-associated infectious complications. Our study may further provide a rationale for the use of Idelalisib as a novel therapeutic option in inflammatory diseases. |
format | Online Article Text |
id | pubmed-8571156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-85711562021-11-08 The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells Braun, Christiane Schlaweck, Sebastian Daecke, Solveig Nora Brossart, Peter Heine, Annkristin Cancer Immunol Immunother Research Report The PI3Kδ-inhibitor Idelalisib is approved for the treatment of Non-Hodgkin lymphoma. However, its use has been decreased within the last years due to deleterious infections such as cytomegalovirus and pneumocystis jirovecii. Here, we have investigated the effect of Idelalisib on human monocyte-derived dendritic cells (DCs) as important players in the induction of immune responses. We found that Idelalisib-treated DCs displayed impaired T cell stimulatory function. PI3Kδ inhibition during differentiation resulted in decreased Interleukin-12, Interleukin-13 and TNFα production by DCs after lipopolysaccharide stimulation. Moreover, DCs showed decreased expression of the activation marker CD83 after Idelalisib treatment. Further, in line with this was the failure of Idelalisib-treated DCs to properly induce allogeneic T cells in a dose-dependent manner. Finally, activation of the NFκB pathway was also ablated in Idelalisib-treated DCs. Our results implicate that severe infectious complications may not only result from direct PI3Kδ-inhibition in T cells, but also from impaired DC function in Idelalisib-treated patients. Here, we provide new insight into the pathogenesis of Idelalisib-associated infectious complications. Our study may further provide a rationale for the use of Idelalisib as a novel therapeutic option in inflammatory diseases. Springer Berlin Heidelberg 2021-06-25 2021 /pmc/articles/PMC8571156/ /pubmed/34173009 http://dx.doi.org/10.1007/s00262-021-02988-3 Text en © The Author(s) 2021 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 | Research Report Braun, Christiane Schlaweck, Sebastian Daecke, Solveig Nora Brossart, Peter Heine, Annkristin The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title | The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title_full | The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title_fullStr | The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title_full_unstemmed | The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title_short | The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells |
title_sort | pi3kδ inhibitor idelalisib impairs the function of human dendritic cells |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8571156/ https://www.ncbi.nlm.nih.gov/pubmed/34173009 http://dx.doi.org/10.1007/s00262-021-02988-3 |
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