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Verfasst von:Faehling, Sebastian [VerfasserIn]   i
 Coelho, Mariana [VerfasserIn]   i
 Floerchinger, Alessia [VerfasserIn]   i
 Schneider, Christof [VerfasserIn]   i
 Stilgenbauer, Stephan [VerfasserIn]   i
 Lichter, Peter [VerfasserIn]   i
 Seiffert, Martina [VerfasserIn]   i
 Rößner, Philipp M. [VerfasserIn]   i
Titel:Simultaneous inhibition of PI3Kgamma and PI3Kdelta deteriorates t-cell function with implications for chronic lymphocytic leukemia
Verf.angabe:Sebastian Faehling, Mariana Coelho, Alessia Floerchinger, Christof Schneider, Stephan Stilgenbauer, Peter Lichter, Martina Seiffert, Philipp M. Roessner
E-Jahr:2023
Jahr:Feb 22, 2023
Umfang:10 S.
Fussnoten:Gesehen am 21.04.2023
Titel Quelle:Enthalten in: HemaSphere
Ort Quelle:[Philadelphia, Pennsylvania] : Wolters Kluwer Health, 2017
Jahr Quelle:2023
Band/Heft Quelle:7(2023), 3, Artikel-ID e840, Seite 1-10
ISSN Quelle:2572-9241
Abstract:Chronic lymphocytic leukemia (CLL) is a common and incurable B-cell malignancy. Recent therapeutic approaches that target the B-cell receptor signaling pathway include inhibition of phosphatidylinositol-3-kinase (PI3K). The PI3K isoform delta is constitutively active in CLL, making it an attractive therapeutic target. However, the expression of PI3K isoforms is not exclusive to leukemic cells, as other immune cells in the tumor microenvironment also rely on PI3K activity. Subsequently, therapeutic inhibition of PI3K causes immune-related adverse events (irAEs). Here, we analyzed the impact of the clinically approved PI3Kδ inhibitors idelalisib and umbralisib, the PI3Kγ inhibitor eganelisib, and the dual-γ and -δ inhibitor duvelisib on the functional capacity of T cells. All investigated inhibitors reduced T-cell activation and proliferation in vitro, which is in line with PI3K being a crucial signaling component of the T-cell receptor signaling. Further, dual inhibition of PI3Kγ and PI3Kδ showed strong additive effects suggesting a role also for PI3Kγ in T cells. Extrapolation of this data to a clinical setting could provide an explanation for the observed irAEs in CLL patients undergoing treatment with PI3K inhibitors. Consequently, this highlights the need for a close monitoring of patients treated with PI3K inhibitors, and particularly duvelisib, due to their potentially increased risk of T-cell deficiencies and associated infections
DOI:doi:10.1097/HS9.0000000000000840
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: https://doi.org/10.1097/HS9.0000000000000840
 kostenfrei: Volltext: https://journals.lww.com/hemasphere/Fulltext/2023/03000/Simultaneous_Inhibition_of_PI3Kgamma_and_PI3Kdelta.8.aspx
 DOI: https://doi.org/10.1097/HS9.0000000000000840
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1843317850
Verknüpfungen:→ Zeitschrift

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