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- W2952388162 abstract "Abstract Adoptive transfer of allogeneic NK cells holds great promise for cancer immunotherapy. There is a variety of protocols to expand NK cells in vitro, most of which are based on stimulation with cytokines alone or in combination with feeder cells. Although IL-15 is essential for NK cell homeostasis in vivo, it is commonly used at supraphysiological levels to induce NK cell proliferation in vitro. As a result, adoptive transfer of such IL-15–addicted NK cells is associated with cellular stress because of sudden cytokine withdrawal. In this article, we describe a dose-dependent addiction to IL-15 during in vitro expansion of human NK cells, leading to caspase-3 activation and profound cell death upon IL-15 withdrawal. NK cell addiction to IL-15 was tightly linked to the BCL-2/BIM ratio, which rapidly dropped during IL-15 withdrawal. Furthermore, we observed a proliferation-dependent induction of BIM short, a highly proapoptotic splice variant of BIM in IL-15–activated NK cells. These findings shed new light on the molecular mechanisms involved in NK cell apoptosis following cytokine withdrawal and may guide future NK cell priming strategies in a cell therapy setting." @default.
- W2952388162 created "2019-06-27" @default.
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- W2952388162 date "2019-02-01" @default.
- W2952388162 modified "2023-10-03" @default.
- W2952388162 title "Induction of the BIM Short Splice Variant Sensitizes Proliferating NK Cells to IL-15 Withdrawal" @default.
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- W2952388162 doi "https://doi.org/10.4049/jimmunol.1801146" @default.
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