HOPX is required for the generation of umbilical cord blood-derived memory-like NK cells induced by three cytokines

BackgroundNatural killer (NK) cells represent a highly promising form of cancer immunotherapy. Recent studies have utilized umbilical cord blood (UCB) as a source of NK cells and achieved encouraging results.

However, several challenges remain, including the limited number of NK cells that can be obtained from UCB, as well as the difficulty of ex vivo expansion and functional persistence, which hinder large−scale clinical applications. In addition, the absence of standardized culture systems leads to inconsistent cell purity and cytotoxic activity, thereby limiting the efficacy and translational potential of NK cell−based tumor therapy.MethodWe demonstrated that in vitro activation by a combination of cytokines, followed by prolonged expansion with high doses of IL-2, can induce and expand memory-like NK cells from UCB.

We performed both in vivo and in vitro investigations into the unique properties of these memory-like NK cells, and analyzed their heterogeneity via single-cell sequencing.ResultsThese memory-like NK cells displayed augmented proliferation and sustained cytotoxic efficacy. Via single-cell analysis, we detected considerable heterogeneity among UCB-derived NK cells.