New research from the University of Oklahoma demonstrates how an aggressive form of breast cancer co-opts the body's immune system to attract nerves that fuel tumor growth, according to an Aug. 4 announcement.
The study, published in Cell Death & Differentiation, investigates triple-negative breast cancer, a type known for being difficult to treat. Scientists have previously observed networks of nerves within many solid tumors but had not understood how those nerves arrive at the tumor site.
Researchers found that tumors recruit macrophages—immune cells typically responsible for fighting infection and healing wounds. Once inside the tumor, these macrophages release brain-derived neurotrophic factor (BDNF), a protein that acts as a chemical beacon encouraging nearby nerves to grow into the tumor. While BDNF is primarily recognized for its role in nerve cell growth in the brain, this research shows that breast tumors use it to attract nerves supporting their own growth and resistance to treatment.
The findings suggest a potential new treatment strategy: blocking communication between macrophages and nerves rather than targeting cancer cells directly. Cox and her team tested this approach in mice by using a drug already on the market to block BDNF signaling. "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."
To determine whether these results might apply to humans, Cox's team analyzed data from patients with triple-negative breast cancer and found higher levels of macrophages and BDNF were associated with poorer survival outcomes. This suggests similar mechanisms may be present in people as observed in mice.
Cox said her next steps include further investigating how nerves cause tumor growth—potentially by encouraging blood vessel formation or enabling metastasis—and testing interventions in high-grade ovarian cancer as well. "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.
