Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Braun, C; Schlaweck, S; Daecke, SN; Brossart, P; Heine, A.
The PI3Kδ inhibitor idelalisib impairs the function of human dendritic cells
CANCER IMMUNOL IMMUN. 2021; 70(12): 3693-3700.
Doi: 10.1007/s00262-021-02988-3
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- Führende Autor*innen der Med Uni Graz
- Heine Annkristin
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- Abstract:
- The PI3K delta-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. PI3K delta inhibition during differentiation resulted in decreased Interleukin-12, Interleukin-13 and TNF alpha 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 NF kappa B pathway was also ablated in Idelalisib-treated DCs. Our results implicate that severe infectious complications may not only result from direct PI3K delta-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.
- Find related publications in this database (Keywords)
- Idelalisib
- Infection
- Dendritic cells
- PI3K delta