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Updated: May 12, 2026
Flow Cytometry-based Assay for the Monitoring of NK Cell Functions
Published on: October 30, 2016
Modulation of natural killer cell effector functions through lenalidomide/dasatinib and their combined effects
Isabel Jungkunz-Stier1, Michael Zekl, Thorsten Stühmer
1Immune Recovery Section, Division of Hematology.
Abstract:
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-γ (IFNγ), but not of tumor necrosis factor-α (TNFα). 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 TNFα. 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.
Insights
Dasatinib and lenalidomide combination therapy showed limited impact on multiple myeloma (MM) cell viability. Lenalidomide enhanced natural killer (NK) cell activity, but dasatinib did not support this effect.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Dasatinib, a multikinase inhibitor, targets Src kinases in multiple myeloma (MM).
- Natural killer (NK) cells play a role in anti-cancer immunity.
- Lenalidomide is a known immunomodulatory drug used in MM treatment.
Purpose of the Study:
- To investigate the combined effects of dasatinib and lenalidomide on MM cell viability.
- To evaluate the impact of this combination on NK cell effector functions.
Main Methods:
- Assessing MM cell line and primary cell viability upon drug treatment.
- Measuring NK cell degranulation (CD107a/b), cytokine production (IFNγ, TNFα), and cytotoxicity.
- Analyzing the role of the TRAIL/TRAIL-R system in NK cell responses.
Main Results:
- The drug combination had minimal effect on MM cell viability.
- Lenalidomide alone enhanced NK cell effector functions, including cytotoxicity against MM cells.
- Dasatinib did not augment, and sometimes attenuated, lenalidomide-induced NK cell activity and cytotoxicity.
- Lenalidomide-mediated NK cell cytotoxicity was linked to TRAIL expression.
Conclusions:
- Lenalidomide enhances NK cell activity against MM cells via the TRAIL/TRAIL-R pathway.
- Dasatinib is not suitable for combination with lenalidomide to boost NK cell-mediated anti-MM effects.
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