Scientists, part-funded by Worldwide Cancer Research, have uncovered a promising new treatment approach that in the future could improve survival for the most common type of childhood brain tumour - called medulloblastoma.
The research, carried out by a large collaborative group of cancer researchers from around the world, has shown that combining immunotherapy with a drug called TNF (tumour necrosis factor) could eradicate tumours that were otherwise unaffected by immunotherapy.
This ground-breaking research, although still in its early stages, has left scientists hopeful that clinical trials can be started as soon as possible to test the treatment combination in patients.
Although advances in surgery, radiotherapy and chemotherapy have improved survival for children with medulloblastoma, approximately 1 in 3 patients remain incurable. And those that survive often suffer long term side effects of treatments that impact the developing brain.
Targeted treatments, such as immunotherapy, can have less toxic side effects and could improve outcomes for these patients. However, not all patients benefit from immunotherapy due to genetic differences between tumours.
A better understanding of why this is the case will help researchers develop ways to make immunotherapy work for more people.
For some types of immunotherapy to work, the patient’s immune system must be able to detect cancer cells and eradicate them like it would against invading bacteria or viruses.
Some cancers can hide from the immune system because they are missing a molecule that scientists call MHC-1. This molecule normally sits on the surface of the cell and acts like a signal flare telling the immune system that something wrong with the cell and needs destroying.
With this molecule missing, cancer cells have an invisibility cloak that keeps them hidden from the immune system.
In this study, scientists discovered that the drug TNF could force MHC-1 back to the surface of these cancer cells, effectively stripping them of their invisibility cloak and making them open to attack from the immune system.
When they combined TNF with immunotherapy in mice with brain cancer, they discovered that brain tumours were melting away.
Our findings suggest that some cancers may not respond to immunotherapy because the tumours don't have sufficient MHC-1 levels to trigger an effective immune response. Our hope is that in the near term, combining immunotherapy with TNF will increase the effectiveness of immunotherapy for children who are battling brain cancer.
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