How the Immune System Drives Nerve Growth in TNBC

Nerve involvement in tumors—known as axonogenesis—has been documented across several cancer types, but the mechanisms that drive nerve growth into triple-negative breast cancer (TNBC) have remained poorly understood. In this video, study authors Maureen A. Cox, PhD, and Jumana Abbadi, MD, of the University of Oklahoma Health Sciences Center, discuss findings from their recent paper in Cell Death & Differentiation examining how nerves are recruited into TNBC tumors.

Cox describes the rationale for the study, noting that TNBC lacks the hormone receptor–driven treatment options available in other breast cancer subtypes, leaving surgery and chemotherapy as the primary options for many patients. Because immunotherapy has shown limited benefit in TNBC, the team hypothesized that tumor-infiltrating nerves might be suppressing the anti-tumor immune response.

The central finding, according to Cox, overturns a long-standing assumption in the field: it is not the tumor cells themselves but tumor-associated macrophages that supply the brain-derived neurotrophic factor (BDNF) responsible for drawing nerves into the tumor. The tumor manipulates these macrophages, prompting them to express BDNF and support nerve ingrowth.

Abbadi discusses how genetically removing macrophage-derived BDNF selectively reduced the growth of sensory nerves into tumors, without affecting sympathetic innervation and how chemically depleting those sensory nerves also slowed tumor growth. Together, the data identify sensory innervation, driven by macrophage-secreted BDNF, as a specific and targetable contributor to TNBC progression.

Cox also points to an existing class of drugs—TrkB inhibitors—that target this signaling pathway but are currently approved only for tumors with specific gene fusions. In their mouse models, these drugs blocked both tumor innervation and tumor growth, suggesting the approach could have broader relevance for TNBC patients beyond that narrow population.

Watch the full conversation for more on how macrophage-derived BDNF shapes the tumor microenvironment in TNBC.

REFERENCE

Abbadi J, Velayutham R, Annan AC, et al. Macrophage-secreted brain-derived neurotrophic factor promotes tumor growth in triple-negative breast cancer by inducing axonogenesis. Cell Death Differ. doi.org/10.1038/s41418-026-01796-5