Deadly brain cancer found to erode skull, alter immune response: Study
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New Delhi: Glioblastoma, the most aggressive form of brain cancer, affects far more than the brain itself, with new research showing that it can erode the skull, reshape skull marrow, and disrupt the body’s immune system.
A study by scientists at the Montefiore Einstein Comprehensive Cancer Center (MECCC) and Albert Einstein College of Medicine has provided the first evidence of such changes. The findings, published in Nature Neuroscience, also revealed that drugs designed to prevent skull-bone loss may worsen the disease.
“Our discovery that this notoriously hard-to-treat brain cancer interacts with the body's immune system may help explain why current therapies -- all of them dealing with glioblastoma as a local disease -- have failed, and it will hopefully lead to better treatment strategies,” said corresponding author Jinan Behnan, Assistant Professor in the Department of Neurological Surgery and the Department of Microbiology and Immunology at Einstein.
Glioblastoma patients undergoing surgery, chemotherapy and radiation currently have a median survival of about 15 months.
The researchers used advanced imaging on mice with glioblastoma and found that the tumours caused skull bones to erode, particularly along sutures where skull bones fuse. CT scans of patients with glioblastoma showed similar thinning of skull bones in the same regions.
These erosions increased the number and size of skull-to-brain channels, which the team suggested might enable tumours to send signals to skull marrow and alter its immune environment. They observed that glioblastoma activated genes in skull marrow that spurred production of inflammatory immune cells, while in femur marrow it suppressed genes required to produce other key immune cells.
Notably, treatment with US FDA-approved anti-osteoporosis drugs, zoledronic acid and denosumab, prevented skull erosion. However, zoledronic acid accelerated tumour growth in one type of glioblastoma, and both drugs interfered with the benefits of immunotherapy (anti-PD-L1), which boosts tumour-fighting T cells.
The study highlights glioblastoma’s complex interactions with the immune system and suggests the need for new approaches that consider its effects beyond the brain.