New research has provided insight into the biological mechanisms that may contribute to poor outcomes in some cases of neuroblastoma. 

A high-risk form of the disease that is difficult to treat is often associated with mutations in the ATRX gene, which controls the expression of multiple sections of the genome and plays a part in children’s development. 

The team, led by scientists at The Institute of Cancer Research, London, uncovered how common ATRX alterations affect the tumour immune microenvironment (TIME). 

Currently, all children with high-risk neuroblastoma receive chemotherapy and an anti GD-2 antibody, but the chance of survival is only about 50%. ATRX alterations affect about 10% of these patients. 

The team used multiple investigative techniques, working with mouse models, cell lines with different types of ATRX mutations, sequencing datasets and patient samples. 

They were able to show that mutations in the ATRX gene lead to the activation of inflammation pathways, which increases the recruitment of macrophages into the tumour, promoting the survival of cancerous cells. 

The scientists demonstrated that the level of immune cell infiltration in tumour samples with ATRX alterations was much higher than that in other subtypes of neuroblastoma. 

Dr Sally George, senior author and Group Leader of the Developmental Oncology Group at the ICR and Honorary Consultant Paediatric Oncologist at The Royal Marsden NHS Foundation Trust, said: “More research is needed to translate these findings into a better understanding of how differences in the TIME relate to response to immunotherapy and other agents, but we hope that this insight will contribute to improving outcomes in the future. 

“We are committed to working towards being able to offer each patient targeted treatment based on the genetics of their cancer, which we believe would save many children’s lives each year.”

Diana Spencer, Senior Digital Content Editor, DDW