Encouraging results from the study investigating the role of Enhancer of Zeste homolog 2 (EZH2) and Natural Killer cells in Neuroblastoma

“Big things often have small beginnings,” said Benjamin Franklin and this looks to be the case with Dr Jinhui Gao’s small grant award of £5,000 investigating the benefit of combining EZH2 inhibitors and anti-GD2 immunotherapy.

In 2023, Dr Gao, working with Prof Juliet Gray and Dr Zoë Walters at the University of Southampton, aimed to determine the role of natural killer cell- mediated anti-tumour effects in neuroblastoma, after treatment with EZH2. The objectives of the study were to look at the correlation between EZH2 protein expression and the surface expression of natural killer ligands in neuroblastoma cells, and to determine if the natural killer cells induced cytotoxicity that could be enhanced in the neuroblastoma cell lines with EZH2 inhibitors.

Currently, intensive chemotherapy used in the treatment for high-risk neuroblastoma does not cure all children and has significant side effects and long-term toxicity, so it is imperative that we continue to look for new treatments. One area is to improve the efficacy of immunotherapy. Anti-GD2 immunotherapy is now a mainstay in the therapy of neuroblastoma and to enhance its effectiveness, this project looked to promote the tumour killing abilities of natural killer cells. Natural killer cells play a major role in the effectiveness of anti-GD2 immunotherapy and EZH2 alters the action of natural killer cells.

The results of the study are encouraging and provide a solid foundation suggesting that this new class of drug, EZH2 inhibitors, have favourable effects on the immune cells in neuroblastoma so that they do have the potential to enhance the effects of anti GD2. The combination of enhancing differentiation and enhancing immunity make this an exciting research avenue to now explore in more depth and has the potential to become another treatment strategy in the future.