Researchers at Baylor College of Medicine, the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital and collaborating institutions show in Nature Cancer that stroke promotes glioma growth and uncovered cellular and molecular mediators involved in the process, linking brain injury to malignant brain tumors.
“Epidemiological and clinical studies suggest that patients with a history of stroke or traumatic brain injury are at increased risk of developing brain tumors. The risk can be about three-fold to seven-fold, depending on the age and sex of the patient,” said corresponding author Dr. Hyun Kyoung Lee , associate professor of pediatrics – neurology and member of the Dan L Duncan Comprehensive Cancer Center at Baylor. Lee also is an investigator at the Duncan NRI.
“Despite these clinical observations, the mechanism that connects brain injury and cancer remains unclear. In the current study, we worked with human and mouse models to investigate whether stroke promotes glioma growth and the factors mediating the connection,” Lee said.
First authors of this work, Dr. Qi Ye and graduate student Christine Madamba from the Lee lab, focused on one type of brain injury, stroke, and on a specific type of brain tumor, glioma, the most prevalent and aggressive malignant brain tumor in adults with a 5-year survival rate.
“We show that stroke promoted tumor infiltration into injured brain regions in human and mouse glioma models, and reduced overall survival,” Lee said. “Looking closer into the cellular and molecular makeup of the tumors, we found that stroke triggers remodeling of the tumor microenvironment.”
The team discovered the emergence of a distinct population of brain cells – tumor-associated astrocytes (TAAs) – with distinct physiological and molecular characteristics, including diminished calcium activity. TAAs were accompanied by the accumulation of two other cell types, remodeled tumor-associated microglia and immune cells called macrophages (TAMs).
Restoring TAA calcium signaling or removing TAMs suppressed stroke-induced glioma progression, identifying both populations as critical mediators of the stroke response. The findings suggest that these injury-induced, tumor-promoting pathways are potential therapeutic targets and support continuing research into strategies that could reduce the risk of glioma growth in patients with a history of brain injury.
“Our study supports that brain injury can be a risk factor for brain cancer. In addition, our findings contribute to growing evidence pointing at a role of astrocytes in brain tumor growth,” Lee said. “Neuron-tumor interactions have been shown to contribute to cancer growth. We show that other brain cells, astrocytes, also seem to communicate with brain cancer cells and influence their behavior. They should be considered when studying cancer mechanisms and therapies.”
Other contributors include Junsung Woo, Tiffany J. Choy, Kate Wheeler, Jiangshan Zhan, Carlo D. Cristobal, Catalina Spjut, Donghui Shin, Juyeon Jo, Roshan R. Ailani, Joshua Smith, Khatri Latha, Akdes Serin Harmanci, Hari Krishna Yalamanchili, Marco Gallo, Kyuson Yun, Yana K. Reshetnyak, Eunhee Kim, Yongsoo Kim, Ganesh Rao and Benjamin Deneen. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, Duncan NRI at Texas Children’s Hospital, Virginia Tech FBRI Cancer Research Center, Virginia Tech, Pennsylvania State University, Houston Methodist Research Institute, Weill Cornell Medical College, University of Rhode Island and the University of Texas Health Science Center at Houston.
For a complete list of the financial support sources for this work, see the publication .
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Nature Cancer
Experimental study
Animals
Stroke drives glioma progression through the emergence of tumor-associated astrocytes with reduced Ca2+ activity
25-Sep-2026