Scientists have discovered that glioblastoma—the deadliest form of brain cancer—does more than attack the brain.
New research from Montefiore Einstein Comprehensive Cancer Center (MECCC) and Albert Einstein College of Medicine shows that the cancer also erodes the skull, alters immune cells in the skull’s bone marrow, and makes it harder for the body to fight back.
These groundbreaking findings, published in *Nature Neuroscience*, suggest that glioblastoma isn’t just a local brain issue—it affects the entire immune system.
“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,” said lead researcher Jinan Behnan, Ph.D. “This new understanding could lead to better treatment strategies.”
About 15,000 people are diagnosed with glioblastoma every year in the U.S., and standard treatments only offer a median survival of 15 months.
Dr. Behnan’s team turned their attention to the skull—specifically its bone marrow, which plays a key role in the immune system. Using imaging on mice, they found that glioblastoma causes erosion in the skull, especially at fusion points between skull bones.
This erosion is unique to malignant brain tumors like glioblastoma and doesn’t appear in other brain conditions like strokes. CT scans of human glioblastoma patients confirmed similar skull thinning.
The research team also found that the erosion opened up tiny channels between the skull marrow and the brain, creating a direct path for immune cells to move. Glioblastoma used this route to change the balance of immune cells in the skull marrow. The number of inflammatory neutrophils doubled, while beneficial B cells nearly disappeared.
“These pro-inflammatory cells flood into the tumor from the skull marrow, making glioblastoma more aggressive,” said co-author E. Richard Stanley, Ph.D.
Interestingly, the femur’s bone marrow reacted differently. In the skull, glioblastoma triggered inflammation. In the femur, it suppressed immune activity—further proof that glioblastoma disrupts the body in complex, systemic ways.
To see if bone-protecting drugs could help, the researchers gave mice two FDA-approved osteoporosis drugs: zoledronic acid and denosumab. Both stopped the skull erosion. However, one of them—zoledronic acid—made one type of glioblastoma grow faster.
Both drugs also reduced the effectiveness of an immunotherapy drug (anti-PD-L1), which normally boosts the immune system’s response to cancer.
This finding suggests that protecting the skull bone may unintentionally interfere with the immune system’s ability to fight glioblastoma. Future treatments might need to strike a balance—reducing harmful inflammation while preserving the immune system’s ability to attack tumors.
The discovery opens the door to new treatments that consider glioblastoma’s impact beyond the brain and could pave the way for better outcomes for patients facing this devastating disease.
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