New Study Reveals How Triple-Negative Breast Cancer Manipulates Immune Cells to Promote Nerve Growth
Research from the University of Oklahoma has shed light on the mechanisms by which aggressive triple-negative breast cancer is able to manipulate the immune system to attract nerves into tumors, potentially aiding cancer growth. Published in the journal Cell Death & Differentiation, the study elucidates the process behind nerve infiltration in these particularly challenging cancers.
The investigation found that tumors recruit macrophages, a type of immune cell typically involved in combating infections and repairing tissue. Once these macrophages enter the tumor microenvironment, they release brain-derived neurotrophic factor (BDNF), a protein known for its role in supporting nerve cell growth in the brain but exploited by tumors to promote nerve growth within the cancerous mass.
“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,” explained Dr. Maureen Cox, assistant professor in the Department of Microbiology and Immunology at the OU College of Medicine.
The findings suggest that the presence of nerves within tumors could contribute to cancer progression and resistance to treatment strategies, signaling a need to explore alternatives to traditional cancer therapies. Cox and her team tested a drug that blocks BDNF signaling in mice, successfully preventing nerve growth into the tumors and significantly slowing tumor advancement. “It looks really promising that we can use this drug, which is already on the market, to target BDNF,” she remarked.
Furthermore, by analyzing data from patients with triple-negative breast cancer, the researchers observed a correlation between elevated levels of macrophages and BDNF and lower survival rates, indicating that this mechanism might be applicable beyond animal models.
Dr. Cox’s team aims to further discern the precise roles that nerves play in tumor development, with preliminary evidence suggesting they may stimulate blood vessel formation, which supplies tumors with critical oxygen and nutrients. Additionally, the researchers intend to explore the implications of this signaling pathway in other aggressive cancers such as high-grade ovarian cancer.
“Ultimately, we want to turn the anti-tumor immunity back on in cancer patients so their own immune systems can reject the tumors,” Dr. Cox stated.
This research was supported by the National Institute of General Medical Sciences of the NIH, Oklahoma’s Tobacco Settlement Endowment Trust, and the Oklahoma Shared Clinical and Translational Resources.
