Defects in NK cell immunity of pediatric cancer patients revealed by deep immune profiling

Systemic immunity plays an important role in cancer immune surveillance and response to therapy, but little is known about the immune status of children with solid cancers. We performed a high-dimensional single-cell analysis of systemic immunity in 50 treatment-naïve pediatric cancer patients, comparing them to age-matched healthy children. Children with cancer had a lower frequency of peripheral NK cells, which was not due to tumour sequestration, had lower surface levels of activating receptors and increased levels of the inhibitory NKG2A receptor. Furthermore, the NK cells of pediatric cancer patients were less mature and less cytotoxic when tested in vitro. Culture of these NK cells with interleukin-2 restored their cytotoxicity. Collectively, our data show that NK cells in pediatric cancer patients are impaired through multiple mechanisms and identifies rational strategies to restore their functionality.