期刊
LEUKEMIA & LYMPHOMA
卷 55, 期 1, 页码 168-176出版社
INFORMA HEALTHCARE
DOI: 10.3109/10428194.2013.794270
关键词
NK cell; multiple myeloma; dasatinib; tyrosine kinase inhibitor; IMiD (R); lenalidomide
资金
- Deutsche Krebshilfe [2009.944.1]
- Deutsche Forschungsgemeinschaft [KFO 216]
- Senator Kurt und Inge Schuster-Stiftung
The multikinase inhibitor dasatinib blocks the constitutive activation of oncogenic Src kinases in multiple myeloma (MM) cells and potentially enhances natural killer (NK) cell activity. Therefore, we tested combination effects of dasatinib and lenalidomide regarding MM cell viability and NK cell effector functions. The drug combination mostly had little influence on the viability of MM cell lines, and produced mixed results on primary MM cells. Prolonged lenalidomide treatment enhanced NK cell effector functions, and dasatinib addition at late stages of NK cell expansion increased levels of CD107a/b and interferon-gamma (IFN gamma), but not of tumor necrosis factor-alpha (TNF alpha). Additive effects were observed for the enhancement of cytokine production and degranulation, but only lenalidomide increased NK cell cytotoxicity against MM cells. This effect correlated with increased TNF-related apoptosis-inducing ligand (TRAIL) expression and was attenuated by dasatinib, or suppressors of TRAIL or TNF alpha. Our data thus indicate a functional role for the TRAIL/TRAIL-R system in lenalidomide-mediated NK-cell activity against MM cells, but also show that dasatinib is unsuitable to support or boost this effect.
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