GSK3 Inhibition Drives Maturation of NK Cells and Enhances Their Antitumor Activity.

ABSTRACT: Maturation of human natural killer (NK) cells as defined by accumulation of cell-surface expression of CD57 is associated with increased cytotoxic character and TNF and IFNγ production upon target-cell recognition. Notably, multiple studies point to a unique role for CD57⁺ NK cells in cancer immunosurveillance, yet there is scant information about how they mature. In this study, we show that pharmacologic inhibition of GSK3 kinase in peripheral blood NK cells expanded ex vivo with IL15 greatly enhances CD57 upregulation and late-stage maturation. GSK3 inhibition elevated the expression of several transcription factors associated with late-stage NK-cell maturation including T-BET, ZEB2, and BLIMP-1 without affecting viability or proliferation. When exposed to human cancer

SUBMITTER: Cichocki F 

PROVIDER: S-EPMC5645243 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature