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Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK Cells
Published on: February 2, 2011
NK92 cells and peripheral blood NK cells respond oppositely upon dasatinib treatment
Fengqi Li1,2, Zhongyi Wang1,2, Dongpeng Zheng1,2
1School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Abstract:
Natural killer (NK) cell is a valuable tool for immunotherapy in cancer treatment, both the cultured cell line NK92 and primary NK cells are widely studied and used in research and clinical trials. Clinical observations witnessed the improvement of patients' NK cells in terms of cell counts and cytotoxic activity upon dasatinib treatment, an approved drug for chronic myeloid leukaemia and Ph+ acute lymphocytic leukaemia. Several studies supported the clinical observations, yet others argued a detrimental effect of dasatinib on NK cells. Due to the complex conditions in different studies, the definite influence of dasatinib on NK92 and primary NK cells remains to be settled. Here, we used a well-defined in vitro system to evaluate the effects of dasatinib on NK92 cells and peripheral blood (PB)-NK cells. By co-culturing NK cells with dasatinib to test the cell counts and target cell-killing activities, we surprisingly found that the chemical influenced oppositely on these two types of NK cells. While dasatinib suppressed NK92 cell proliferation and cytotoxic activity, it improved PB-NK-killing tumour cells. RNA sequencing analysis further supported this finding, uncovering several proliferating and cytotoxic pathways responding invertedly between them. Our results highlighted an intrinsic difference between NK92 and PB-NK cells and may build clues to understand how dasatinib interacts with NK cells in vivo.
Insights
Dasatinib differentially affects natural killer (NK) cells. While suppressing NK92 cell lines, it enhances primary peripheral blood (PB)-NK cell anti-cancer activity, revealing distinct cellular responses.
Area of Science:
- Immunology
- Pharmacology
- Cancer Research
Background:
- Natural killer (NK) cells are crucial for cancer immunotherapy.
- Dasatinib's impact on NK cells is debated, with conflicting reports on its effects.
- Understanding dasatinib's precise influence on different NK cell types is essential for optimizing cancer treatment.
Purpose of the Study:
- To investigate the in vitro effects of dasatinib on NK92 cell lines and primary peripheral blood (PB)-NK cells.
- To clarify the contradictory findings regarding dasatinib's influence on NK cell function.
- To elucidate the differential responses of NK92 and PB-NK cells to dasatinib treatment.
Main Methods:
- Co-culturing NK92 and PB-NK cells with dasatinib.
- Assessing NK cell counts and cytotoxic activity against tumor cells.
- Performing RNA sequencing to analyze molecular pathways.
Main Results:
- Dasatinib suppressed proliferation and cytotoxicity in NK92 cells.
- Dasatinib enhanced the tumor cell-killing activity of PB-NK cells.
- RNA sequencing revealed opposing pathway responses between NK92 and PB-NK cells.
Conclusions:
- Dasatinib exhibits opposing effects on NK92 and PB-NK cells.
- Significant intrinsic differences exist between NK92 cell lines and primary PB-NK cells.
- These findings provide insights into dasatinib's complex interaction with NK cells in vivo.

