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Natural Killer Cells: A Potential Therapy for Paediatric Brain Tumours

Coral Fairhead, Hisaki Fujii, Zhi-Juan Luo, Hye Jin Kim and R Maarten Egeler

Natural killer cells are innate immune cells that are naturally involved in tumour immunosurveillance. These cells have direct cytotoxic activity and also secrete proinflammatory cytokines upon activation. The activation of natural killer cells’ cytolytic activity is dependent on a balance between inhibitory signals and activating signals provided by the host cells. Natural killer cells do not exert their activity on healthy cells, due to interactions of inhibitory receptors with self major histocompatibility class I. Inhibition may be overcome when the cell binds tumour-associated antigens on the surface of tumour cells, resulting in the polarized release of cytolytic granules toward the target cell. Natural killer cells demonstrate particular promise for cellular therapy, as they can identify and eliminate tumours that have altered major histocompatibility class I expression. Central nervous system tumours are the second most common paediatric cancer and are associated with a high mortality rate. Many of these high-grade paediatric brain tumours have very dismal prognoses, despite standard treatment regimens, and patients would substantially benefit from a novel type of therapy. Natural killer cells have been shown to be effective against many human malignancies; however, less is known about their efficacy against brain tumours. Treatment of medulloblastoma and adult glioblastoma with natural killer cells has been investigated previously and yielded promising results. Natural killer cells represent a small fraction of peripheral blood, which poses a limitation for their widespread use in adoptive cell therapy. Current research is focussed on establishing an optimal protocol for the ex vivo expansion and activation of natural killer cells. In the future, paediatric brain tumours such as glioblastoma multiforme, ependymoma and atypical teratoid/rhabdoid tumours should be examined for their susceptibility to natural killer cells.