New research from the University of Oklahoma has revealed how an aggressive type of breast cancer can manipulate the immune system to draw nerves into tumors, creating conditions that may help the cancer grow. Scientists have known for years that many solid tumors contain extensive nerve networks. What has been less clear is how those nerves enter the tumor in the first place.
The new study, published in Cell Death & Differentiation, provides an explanation for this process in triple-negative breast cancer, a particularly difficult form of the disease to treat. Immune Cells Help Draw Nerves Into Tumors The researchers discovered that tumors attract macrophages, a type of immune cell that normally helps the body fight infections and repair damaged tissue. After entering the tumor, these macrophages release brain-derived neurotrophic factor (BDNF), a protein that encourages nearby nerves to grow toward and into the cancer.
BDNF is most widely known for supporting the growth and survival of nerve cells in the brain. In breast cancer, however, the researchers found that tumors can take advantage of this same biological signal. By prompting nerve growth inside the tumor, the process may contribute to cancer progression and resistance to 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. The discovery could open the door to a different way of treating cancer.
Instead of focusing only on destroying cancer cells, future therapies might interrupt the signaling between macrophages and the nerves that appear to support tumor growth. Cox and her colleagues tested this strategy in mice. They used a drug that blocks BDNF signaling and found that nerves no longer grew into the tumors.
Tumor growth was also 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." Evidence From Triple-Negative Breast Cancer Patients The researchers also examined data from people with triple-negative breast cancer to determine whether the same biological pattern might occur in humans.
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