Breast Cancer Hijacks Immune Cells to Recruit Tumor-Fueling Nerves, OU Study Reveals
Key Insights
University of Oklahoma researchers discovered that triple-negative breast cancer (search) recruits macrophages to release BDNF, a protein that attracts nerves into tumors to fuel growth.
Blocking BDNF signaling with an existing drug significantly reduced nerve infiltration and tumor growth in mouse models.
Analysis of patient data showed that higher levels of macrophages and BDNF in tumors were associated with poorer survival outcomes.
New research from the University of Oklahoma has uncovered how an aggressive form of breast cancer exploits the body's own immune system to attract nerves that fuel tumor growth, revealing a potential new therapeutic vulnerability.
The study, published in Cell Death & Differentiation, demonstrates that triple-negative breast cancer (search) — a notoriously difficult-to-treat subtype — recruits macrophages, immune cells that normally aid in fighting infection and healing wounds, and repurposes them to draw nerves into the tumor microenvironment.
"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., 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 (search).
How Tumors Hijack a Neural Growth Signal
Scientists have long observed that many solid tumors contain networks of nerves, but the mechanism by which those nerves infiltrate tumors has remained unclear. The OU team found that once macrophages are recruited into the tumor, they release a protein called brain-derived neurotrophic factor (BDNF) (search). Though BDNF is best known for its role in helping nerve cells grow in the brain, breast tumors hijack this same signal, using it as a chemical beacon that encourages nearby nerves to grow into the tumor mass.
These infiltrating nerves, in turn, support tumor growth and contribute to treatment resistance. The researchers believe the nerves are immunosuppressive, potentially blunting the body's natural anti-tumor immune response.
Blocking BDNF Shows Promise in Preclinical Models
Cox and her team tested a therapeutic intervention in mouse models by using a drug to block BDNF signaling. The results were striking: nerves failed to infiltrate the tumor, and tumor growth was significantly reduced.
"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."
Clinical Relevance Confirmed in Patient Data
To assess whether these preclinical findings might translate to humans, the research team analyzed data from patients with triple-negative breast cancer (search). They found that tumors with higher levels of macrophages and BDNF were associated with poorer survival, suggesting that the same biological mechanism observed in mice may also operate in human disease.
Future Directions and Broader Implications
The findings point toward a fundamentally different treatment paradigm: rather than targeting cancer cells directly, future therapies could aim to block the communication between macrophages and the nerves that help tumors thrive.
Cox's next steps include further investigating precisely how nerves promote tumor growth. Some evidence suggests that nerves encourage the growth of blood vessels that deliver oxygen and nutrients to the tumor, while other studies indicate that tumor cells may crawl along nerves to escape the original site and metastasize. She also plans to test the BDNF-blocking intervention in high-grade ovarian cancer (search), which shares similar treatment challenges with triple-negative breast cancer (search).
"Ultimately, we want to turn the anti-tumor immunity back on in cancer patients so their own immune systems can reject the tumors," Cox said.