Neurons and immune cells work together to promote tumor growth in neurofibromatosis type 1, research in mice suggests.
Children with NF1 can develop brain and nerve tumors. If a tumor develops within the optic nerve, which connects the eye and the brain, the child may lose his or her vision.
The new research indicates that nearby noncancerous neurons and immune cells drive the growth of brain tumors in neurofibromatosis—and targeting those immune cells slows the tumor growth.
The findings point to new potential treatments for low-grade brain tumors in people with NF1, the researchers say.
“The fact that nerve cells and immune cells interact to support a tumor is a new way of thinking about how tumors develop and thrive,” says senior author David H. Gutmann, professor of neurology at Washington University School of Medicine in St. Louis and director of the Washington University Neurofibromatosis Center.
“We have to consider nerve cells as participants, if not essential drivers, of cancer development.”
“These tumors are arising in the nervous system, but until recently, few people had considered that the nerve cells themselves could be playing a role in tumor development and growth.
“These findings show that we have to consider nerve cells as participants, if not essential drivers, of cancer development, says Gutmann, senior author of the paper in Nature Communications.
NF1 affects about one in every 3,000 people. Any one of a variety of mutations in the NF1 gene causes the condition. While people with NF1 usually come to medical attention for birthmarks on their skin, nearly one in five children with NF1 will develop a brain tumor on the optic nerve, called an optic glioma, that can lead to loss of vision.
To better understand what drives the development and growth of these brain tumors in people with NF1, first author Xiaofan Guo, a graduate student in Gutmann’s research laboratory, and colleagues studied mice with NF1 mutations and optic gliomas.
The team previously had discovered that the tumor cells in optic gliomas intersperse with immune cells that help drive tumor formation and growth. But there also exists another cell type in the vicinity of the tumor: neurons.
Suspecting that neurons also might contribute to tumor growth, the researchers examined human neurons with NF1 mutations they had grown from stem cells. They discovered that the neurons release a protein that activates immune cells known as T cells, which then produce proteins that promote the growth of tumor cells.
The findings jibe with data from people with low-grade gliomas. An analysis of two publicly available datasets showed that patients whose tumors had more of a kind of T cell known as CD8+ T cells had reduced overall survival.
Disrupting the communication between neurons, T cells, and tumor cells potentially could slow the growth of tumors, the researchers say.
In the new study, they removed T cells from mice with optic gliomas, or prevented T cells from getting into the brains of such mice. In both scenarios, the researchers found that the optic gliomas grew more slowly in the absence of T cells.
“What we have here is a new way of thinking about how neurons and immune cells interact to control tumor growth, adding important new insights to the emerging field of cancer neuroscience,” Gutmann says.
“We are excited about harnessing these critical interactions to develop new therapeutic strategies for childhood brain tumors.”
The National Institute of Neurological Disorders and Stroke, the McDonnell Center for Cellular and Molecular Neuroscience, and the National Institutes of Health funded the work.
