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Open Access 01-12-2021 | Cytokines | Research Report

The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells

Authors: Christiane Braun, Sebastian Schlaweck, Solveig Nora Daecke, Peter Brossart, Annkristin Heine

Published in: Cancer Immunology, Immunotherapy | Issue 12/2021

Abstract

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.

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Title: The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells
Authors: Christiane Braun
Sebastian Schlaweck
Solveig Nora Daecke
Peter Brossart
Annkristin Heine
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keyword: Cytokines
Published in: Cancer Immunology, Immunotherapy / Issue 12/2021
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-021-02988-3

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