Glioblastoma is a devastating brain tumour that kills three quarters of patients within a year of diagnosis. Current treatments can prolong survival but are not curative.
Whilst immunotherapy treatments have revolutionised outcomes in some cancers, glioblastoma has proved resistant.
In this project, Dr Bulstrode and team are taking forward research focused on a type of immune cell that is associated with this resistance to immunotherapy, to try to overcome this barrier to treatment.
Glioblastoma is an aggressive, invasive brain tumour that grows and spreads quickly. It strikes around 2,500 people every year in the UK, seven people every day. Only a quarter of these patients survive more than a year from diagnosis, and only 5% survive five years.
The current treatment strategy includes surgery to ‘debulk’ the tumour, followed by radiotherapy and chemotherapy to destroy remaining tumour. This prolongs survival but is not curative – the tumour always grows back. Despite many years of research, no treatments have yet been found that can prevent this regrowth.
Read more: About brain tumours
New immunotherapy treatments have revolutionised outcomes in many cancers by priming the body’s immune system to find and destroy cancerous cells. Unfortunately glioblastoma has proved resistant to these treatments.
This resistance to immunotherapy is partly due to immune cells called tumour associated macrophages (TAMs) that are found in large numbers in glioblastoma. TAMs help the tumour to grow, spread and avoid attack by the immune system.
It has been shown in other cancers that TAMS can be turned against the tumour, enhancing the body’s immune attack and generating an immune-hot environment in which immunotherapies are more successful.
Neurosurgeon Harry Bulstrode has shown that TAMs can be harvested from patients' brain tumours at the time of surgery, and he has carried out preliminary work showing that it is possible to modify these cells.
He will now use these techniques to genetically modify these TAMs to either kill them, or to reprogramme them to stimulate anti-tumour activity. As well as studying the effect on individual glioblastoma cells, the team will assess the effect on the full range of cell types that make up a tumour, as well as on healthy brain tissue to understand the safety of the treatment.
Immunotherapy is widely seen as the most promising avenue for improving survival in patients with brain cancer.
In order to deliver this survival benefit, however, it is necessary to overcome the barrier presented by the tumour-supportive TAMs. By using cells that are harvested directly from patients, the team will be able to accurately recapitulate the biology and behaviour of these cells, ensuring the relevance of their work to human patients and facilitating translation towards new treatments that in future could help people like Theo, who died at the age of 50, just five months after being diagnosed with glioblastoma.
Dr Harry Bulstrode is a neurosurgeon at Addenbrooke’s Hospital in Cambridge, where he treats patients with brain tumours and movement disorders. He also runs a lab at the Cambridge Stem Cell Institute, where he pursues his interest in precise brain targeting approaches, and has established the tools, techniques and collaborations necessary to successfully carry out this ambitious project.
His research benefits from having access to the human brain and brain tumour tissue resected as part of his surgical practice, with the necessary permissions in place to enable use of this valuable tissue.
Find out about our other research in this area:
