Triple-negative breast tumors may hijack immune cells to attract nerves that help the cancer grow.
Nerves growing through a tumor may help an aggressive breast cancer survive, expand, and resist treatment. University of Oklahoma researchers have identified how triple-negative breast cancer may recruit those nerves by turning the body’s own immune cells into messengers.
Networks of nerves have been observed in many solid tumors, but their origin has remained uncertain. Research published in Cell Death & Differentiation traces this process in triple-negative breast cancer, a particularly difficult form of the disease to treat.
Immune cells draw nerves into tumors
The investigation focused on macrophages, immune cells that normally fight infections and repair damaged tissue. Triple-negative breast tumors draw these cells into their surroundings, where the macrophages release brain-derived neurotrophic factor (BDNF), a protein that promotes nerve growth.
BDNF is best known for supporting nerve cells in the brain. Inside breast tumors, however, the same signal appears to attract nearby nerves that help the cancer grow and withstand treatment.
“Macrophages are the critical source for drawing nerves into the tumor. Although macrophages typically play a positive role in the body, they are facilitating a negative function in this scenario of breast cancer,” said Maureen Cox, Ph.D., an assistant professor in the Department of Microbiology and Immunology at the OU College of Medicine and a research member of OU Health Stephenson Cancer Center.
Blocking BDNF slowed tumor growth
The mechanism suggests a treatment strategy that does not attack cancer cells directly. Instead, a therapy could interrupt the communication between macrophages and the nerves that support the tumor.
Cox and her colleagues tested this approach in mice using a drug that blocks BDNF signaling. The treatment prevented nerves from entering the tumors and significantly reduced tumor growth.
“It looks really promising that we can use this drug, which is already on the market, to target BDNF,” Cox said. “We believe that the nerves are immunosuppressive, so if we can stop the nerves from growing in the first place, maybe we can boost the immune response to help fight the cancer.”
Patient data support the same pathway
To investigate whether the same process might occur in people, Cox and her colleagues examined data from patients with triple-negative breast cancer. Higher levels of macrophages and BDNF within tumors were associated with poorer survival, supporting the possibility that the pathway observed in mice also operates in humans.
Cox now plans to investigate exactly how nerves promote tumor growth. Existing evidence suggests that they may encourage blood vessels to form, supplying cancer cells with oxygen and nutrients. Other research indicates that tumor cells may travel along nerves as they leave the original site and spread to other parts of the body.
She also intends to test the same intervention in high-grade ovarian cancer, another aggressive disease that remains difficult to treat.
“Ultimately, we want to turn the anti-tumor immunity back on in cancer patients so their own immune systems can reject the tumors,” she said.
Reference: “Macrophage-secreted brain-derived neurotrophic factor promotes tumor growth in triple-negative breast cancer by inducing axonogenesis” by Jumana Abbadi, Rameswari Velayutham, Anand C. Annan, Amin Reza Nikpoor, Maryam Ahmadi, Beatriz G. S. Rocha, Jacob W. Farriester, Jessica M. Reel, Eric C. Holland, Frank Szulzewsky, Alexander Birbrair, Kar-Ming Fung, Sebastien Talbot and Maureen A. Cox, 2 July 2026, Cell Death & Differentiation.
DOI: 10.1038/s41418-026-01796-5
The research was supported by the National Institute of General Medical Sciences of the NIH (award numbers P20GM103447 and P20GM103639).
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