Deadly brain cancer glioblastoma has effects that extend beyond the brain, a new study shows, revealing its ability to erode the skull, alter skull marrow, and influence the body’s immune response. The findings, published in Nature Neuroscience, were made by researchers at Montefiore Einstein Comprehensive Cancer Center and Albert Einstein College of Medicine.
Glioblastomas are the most aggressive form of brain cancer, with patients typically surviving around 15 months after standard treatment, which includes surgery, chemotherapy, and radiation. Until now, therapies have focused on treating the tumour locally, but the study suggests that the disease can impact the immune system through interactions with the skull.
Using advanced imaging in mice with two different glioblastoma types, the researchers observed skull erosion, particularly along the sutures where skull bones fuse. Such erosion appeared specific to glioblastoma and other malignant intracranial tumours, as it did not occur in cases of stroke, other brain injuries, or systemic cancers. CT scans of human patients with glioblastoma revealed similar skull thinning in comparable anatomical regions.
The study found that the skull erosion created channels between the tumour and the skull marrow. Researchers proposed that these channels enable glioblastoma to send signals to the marrow, altering immune cell activity. Gene analysis showed that in skull marrow, glioblastoma activated genes that increase production of inflammatory immune cells. In contrast, marrow in the femur showed suppression of genes required for generating multiple types of immune cells, suggesting that the tumour has systemic effects on immunity.
The researchers also investigated whether anti-osteoporosis drugs could mitigate skull erosion. FDA-approved drugs such as zoledronic acid and denosumab were able to prevent bone loss. However, zoledronic acid accelerated tumour progression in one type of glioblastoma, and both drugs reduced the effectiveness of anti-PD-L1 immunotherapy, which is designed to increase tumour-fighting T cells.
“These findings highlight that glioblastoma is not only a local brain disease but also interacts with the body’s immune system in ways that can influence treatment outcomes,” said Jinan Behnan, Assistant Professor at Einstein College of Medicine and corresponding author of the study.
The study emphasizes the complexity of glioblastoma and the need for treatment strategies that consider its impact beyond the tumour site. Understanding the interactions between the cancer, skull marrow, and systemic immunity could guide future approaches to improve patient outcomes in this notoriously hard-to-treat brain cancer.