One of the most detailed maps to date of meningioma — the most common brain tumour in adults — reveals how the tumour's surrounding environment helps drive disease behaviour and patient outcomes, according to new research from Mayo Clinic.
The study, published in Nature Genetics and conducted in collaboration with scientists at Princess Margaret Cancer Centre in Toronto, combines several advanced laboratory techniques to examine tumours at an unprecedented level of detail, offering clues to why some meningiomas grow slowly while others recur or become more aggressive.
The findings could lead to more precise ways to predict risk and guide treatment decisions.
Growing evidence suggests that traditional grading systems for meningioma do not fully capture the behaviour of these complex tumours, prompting the development of molecular classification tools that more accurately predict which tumours are more likely to recur after surgery.
These new findings build on recent developments by investigating the signal from individual cells rather than whole tumours, demonstrating that the tumour microenvironment — the mix of immune and support cells surrounding the tumour — plays a critical role in shaping outcomes.
"We're seeing that it's not just the tumour cells themselves but the ecosystem around them that influences how these tumours grow and respond to treatment," says Gelareh Zadeh, M.D., Ph.D., a Mayo Clinic neurosurgeon and senior author of the study.
Understanding tumor behavior
An estimated 30,000 to 40,000 people in the U.S. are diagnosed with meningioma each year.
While many tumours are benign, others can recur or become life-threatening, and predicting that risk has remained a major challenge.
In this study, researchers analysed hundreds of tumour samples using techniques that allow them to study individual cells rather than averaging signals across the entire tumour.
Using single-cell sequencing and spatial transcriptomics, the team mapped more than 500,000 individual cells and millions of data points across tumours.
This created a high-resolution "atlas" of the genetic footprint of individual cells and how they differ between aggressive and benign tumours, how they change and evolve over space, and how they interact with other cells in their environment.
"Instead of looking at the tumour as a whole, we can now break it down into its individual components and understand what is driving its behaviour," says Dr. Zadeh.
The researchers identified multiple distinct states of immune cells, particularly myeloid cells, that behave differently depending on the tumour.
Some of these cell states were linked to more aggressive disease, while others were associated with better outcomes.
Implications for patient care
The findings build on earlier work from Mayo Clinic researchers outlining a new era of personalised care for meningioma, where molecular and cellular insights guide clinical decision-making.
This latest study adds a critical layer by showing how the tumour microenvironment contributes to that personalization.
Researchers found that certain immune cell programmes were strongly linked to how quickly tumours returned after treatment.
In some cases, these signals were able to add value to tumour grade and even modern molecular classification systems in their ability to predict patient outcomes, suggesting they could help refine decisions about surgery, radiation or closer follow-up in the future.
The study also showed that these biological signatures may be detectable through noninvasive approaches, such as blood-based biomarkers, raising the possibility of monitoring patients over time without repeated surgery.
"This moves us closer to a future where we can better stratify patients — identifying who needs more aggressive therapy and who may avoid overtreatment," says Dr. Zadeh.
Beyond improving prognostic tools, the research highlights potential therapeutic targets.
By identifying how immune cells and tumour cells communicate, the study points to pathways that could be disrupted to slow tumour growth or enhance treatment response.
Next steps include validating the findings in larger, multicenter cohorts and translating these biological insights into clinical tools and prospective trials.
Source: Mayo Clinic