Paediatric diffuse midline glioma (DMG) is one of the most aggressive childhood brain cancers, characterised by a mutation called H3K27M. These tumours grow in the brainstem, which controls vital functions such as breathing and movement, and typically affect children around the age of seven. Sadly, survival is usually less than one year after diagnosis. Because the tumour is diffuse and located deep in the brain, surgery is not possible, and radiotherapy only provides temporary relief. New therapies are urgently needed.

Our research focuses on microglia. These are the immune cells of the brain. Normally, microglia are essential for healthy brain development, but in DMG they appear to play a harmful role. We have identified a particular subtype, called CD11c+ microglia. These are usually found in developing brain regions that produce myelin (the protective coating around nerves). These cells release growth signals that can drive tumour growth and spread. They also appear to alter the behaviour of immune cells called T cells, switching them off in a process known as “exhaustion”. This prevents them from attacking the tumour. We will study human DMG tissue to confirm these findings and test whether blocking harmful microglia–tumour and microglia–immune interactions could provide urgently needed new treatment options for children.