Groundbreaking finding: glioblastoma interacts with the skull and immune marrow
Scientists from Montefiore Einstein Comprehensive Cancer Center (MECCC) and the Albert Einstein College of Medicine have shown, for the first time, that glioblastoma—one of the deadliest brain cancers—does more than invade brain tissue. The disease also erodes the skull, alters the makeup of skull marrow, and disrupts the body’s immune response. Notably, drugs designed to inhibit skull-bone loss sometimes made the cancer more aggressive, according to findings published in Nature Neuroscience.
The skull erosion finding
In mouse models of glioblastoma, researchers observed erosion of skull bones, particularly along the sutures where skull plates fuse. These erosions were accompanied by an increase in channels connecting the skull marrow to the brain. Importantly, CT scans of glioblastoma patients revealed thinning in the same skull regions, suggesting a conserved mechanism across species.
Skull marrow immune reshaping
Using single-cell RNA sequencing, the team found that glioblastoma dramatically rebalanced the skull marrow’s immune cells toward a pro-inflammatory profile. The tumor boosted inflammatory neutrophils while markedly reducing several types of antibody-producing B cells and other B-cell populations. The researchers propose that the skull-to-brain channels may ferry inflammatory cells from the skull marrow into the tumor, contributing to greater aggressiveness and treatment resistance.
Systemic disease and regional differences
Interestingly, the skull marrow responded differently than bone marrow from the femur. Glioblastoma activated genes in the skull marrow that drive inflammation, whereas the femur marrow showed suppression of genes needed to produce multiple immune cell types. This supports the view that glioblastoma is not solely a local brain tumor but a systemic disease with skull–brain signaling pathways shaping the tumor microenvironment.
Implications for therapy
The findings suggest that successful glioblastoma treatments may need to address the skull marrow’s immune landscape, not just the brain tumor itself. Potential strategies include tempering the production of pro-inflammatory neutrophils and monocytes while restoring the generation of T and B cells. Such approaches could complement standard care—surgery, chemotherapy, and radiation—especially given the tumor’s systemic interactions that help explain why current therapies often fall short.
About the study and the researchers
Lead author Jinan Behnan, Ph.D., and colleagues at Einstein and MECCC report the work in Nature Neuroscience. Co-author E. Richard Stanley, Ph.D., underscores the idea that glioblastoma operates through skull-to-brain signaling, opening new avenues for therapy that target the body-wide immune context of the disease.
Context: glioblastoma in numbers
According to the National Cancer Institute, about 15,000 people are diagnosed with glioblastoma each year. Even with standard treatment—surgery, chemotherapy, and radiation—the median survival remains around 15 months, highlighting the urgent need for innovative approaches that consider the disease’s broader biological reach.
Looking ahead
The study’s insights point toward therapeutic concepts that balance the skull marrow’s immune milieu and potentially disrupt the tumor’s inflammatory network. Ongoing research will determine how these discoveries can be translated into safe, effective strategies for patients in the clinic, moving toward a new paradigm where glioblastoma is addressed as a systemic disease with skull-to-brain interactions.
