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 recognise and eliminate cancerous cells. Unfortunately glioblastoma has proved resistant to these treatments.
This resistance to immunotherapy is partly attributed to immune cells called tumour associated macrophages (TAMs) that are found in large numbers in glioblastoma. TAMs contribute to tumour growth and invasion, and they protect the tumour from 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 likely to succeed.
Neurosurgeon Harry Bulstrode has demonstrated that TAMs can be harvested from patient brain tumours at the time of surgery, and he has carried out a body of preliminary work demonstrating that it is possible to modify these cells.
He will now apply 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 use tumour 'slices' to assess the effect on the full range of cell types that make up a tumour, and normal brain tissue to understand the safety of the treatment.
Immunotherapy is widely seen as the most promising avenue for improving survival in patients with malignant brain tumours. In order to deliver this survival benefit it is necessary to overcome the barrier presented by 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 has established permissions for working with primary human brain and brain tumour tissue resected as part of his surgical practice.
Dr Bulstrode 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.
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