PI3Kδ inhibition modulates regulatory and effector T-cell differentiation and function in chronic lymphocytic leukemia.
Animals
Antineoplastic Agents
/ pharmacology
CD8-Positive T-Lymphocytes
/ drug effects
Cell Differentiation
/ drug effects
Class I Phosphatidylinositol 3-Kinases
/ antagonists & inhibitors
Female
Humans
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Purines
/ pharmacology
Quinazolinones
/ pharmacology
Signal Transduction
T-Lymphocytes, Regulatory
/ drug effects
Tumor Cells, Cultured
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
07
05
2018
accepted:
29
10
2018
revised:
27
09
2018
pubmed:
24
12
2018
medline:
7
9
2019
entrez:
22
12
2018
Statut:
ppublish
Résumé
Targeting B-cell receptor signaling using the PI3Kδ inhibitor idelalisib is a highly effective treatment option for relapsed/refractory chronic lymphocytic leukemia (CLL) patients. In addition to its direct impact on tumor cells, PI3Kδ inhibition can modulate the activity of regulatory T-cells (Tregs) resulting in enhanced anti-tumoral immune functions which may contribute to the success of PI3Kδ inhibitors in cancer therapy. The role of Tregs in CLL and their modulation by PI3Kδ inhibitors was so far poorly understood. Using the Eµ-TCL1 adoptive transfer model of CLL, we show that disease development induces the accumulation of activated and highly immunosuppressive Tregs. Depletion of CD25
Identifiants
pubmed: 30573773
doi: 10.1038/s41375-018-0318-3
pii: 10.1038/s41375-018-0318-3
doi:
Substances chimiques
Antineoplastic Agents
0
Purines
0
Quinazolinones
0
1-phosphatidylinositol 3-kinase p110 subunit, mouse
EC 2.7.1.137
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
PIK3CD protein, human
EC 2.7.1.137
idelalisib
YG57I8T5M0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1427-1438Références
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