Researchers at Oncode Institute and Princess Máxima Center have developed a new human model of the brainstem that is changing how one of the most aggressive childhood brain cancers can be studied.
This human lab model could accelerate new treatments for children with diffuse midline glioma (DMG). Diffuse midline glioma (DMG) is a rare brain tumor that mainly affects children. It grows deep in the brainstem, a region that controls essential functions such as breathing and movement. Because of its location, surgery is not possible. Treatment options are limited, and most children survive less than 18 months after diagnosis.
Progress against DMG has been slow. Very little patient tumor material is available for research, making it difficult to understand how the disease starts, spreads, and resists treatment.
Building the right human model
To overcome this, a research group led by Oncode Investigator Anne Rios created a human brainstem organoid: a tiny, three-dimensional brain tissue grown from stem cells that mimics the region where DMG arises.
When the same genetic mutations found in children were introduced, tumors developed that closely matched real patient tumors: including their aggressive growth and cellular diversity. This provides scientists with an unprecedented, human-relevant model of DMG, offering a powerful platform for discovery.
This means researchers can now follow how DMG develops over time and why it is so resistant to therapy, directly in human tissue.
Anne Rios, senior author, Oncode Investigator at Oncode Institute and Princess Máxima Center for Pediatric Oncology
‘We urgently need better treatment options for children with diffuse midline glioma. With this model, we can study the disease and new treatments in human brain tissue, over long periods, and in ways that reflect what happens in patients. We hope that in the future this brings us one step closer to therapies that are not only powerful, but lasting.’
Testing treatments more intelligently
The model also allows researchers to evaluate upcoming therapies for DMG. The team studied CAR T cell therapy, an experimental immunotherapy that has shown promise in some children with DMG, but with responses that are often short-lived.
Using the same CAR T cells currently used in clinical trials, the researchers observed responses in the organoids that closely mirrored what is seen in patients. Over time, the immune cells became exhausted and lost their ability to control the tumor, helping explain why durable responses remain difficult.
Because the organoids can be maintained for weeks, researchers can now study why treatments fail over time and how they might be improved. This dramatically shortens the path from laboratory discovery to better therapies, ensuring that only the most promising strategies move forward to patients, in this case children. This new model goes beyond understanding the disease. It also allows researchers to test new treatments in a realistic human setting.
Capturing the full tumour environment
By adding microglia, the brain’s own immune cells, the researchers made the model even more realistic. They showed for the first time that these cells can actively reduce the effectiveness of CAR T therapy, pushing them toward exhaustion.
This insight opens new opportunities to improve treatment by addressing the tumour environment.
Impact beyond the laboratory
The impact of this work extends beyond research alone. Better human models reduce costly trial-and-error in drug development and help biotech and pharmaceutical partners make smarter investment decisions. This speeds up innovation. It also helps to reduce the use of laboratory animals for pre-clinical research.
Published in Nature Cancer
This research, published in Nature Cancer, shows how advanced human models can help outsmart even the most challenging cancers. By combining fundamental insight with translational relevance.
