Breast cancer co-opts the immune system to attract nerves that fuel tumor growth

New research from the University of Oklahoma demonstrates how an aggressive form of breast cancer co-opts the body's own immune system to attract nerves that fuel tumor growth.

Scientists have long known that many solid tumors contain networks of nerves, but they haven't understood how those nerves get there. This study, published in Cell Death & Differentiation, explains how that happens in triple-negative breast cancer, a type of cancer that is difficult to treat.

Researchers found that tumors recruit macrophages, immune cells that normally help fight infection and heal wounds. Once inside the tumor, the macrophages release a protein called brain-derived neurotrophic factor (BDNF), which acts like a chemical beacon that encourages nearby nerves to grow into the tumor. Although BDNF is best known for helping nerve cells grow in the brain, the researchers found that breast tumors hijack this same signal to attract nerves that support tumor growth and treatment resistance.

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." 

Maureen Cox, Ph.D., assistant professor, Department of Microbiology and Immunology, OU College of Medicine and research member, OU Health Stephenson Cancer Center

The findings are important because they point to a potential new treatment strategy: Rather than targeting cancer cells directly, future therapies could block the communication between macrophages and the nerves that help tumors grow.

Cox and her team tested such an approach in mice. When they used a drug to block BDNF signaling, the nerves didn't infiltrate the tumor and its 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."

To see whether these findings might apply to people, Cox's team analyzed data from patients with triple-negative breast cancer. They found that tumors with higher levels of macrophages and BDNF were associated with poorer survival, suggesting that what occurs in mice may also take place in humans.

Cox's next steps are to further understand how the nerves cause tumor growth. Some evidence suggests that the nerves encourage the growth of blood vessels that deliver oxygen and nutrients to the tumor. Other studies suggest that tumor cells can crawl along the nerves to escape the original site and metastasize. She also plans to test the intervention in high-grade ovarian cancer, which is similarly 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.