Nociceptor neurons suppress antitumor immunity in breast cancer

Here we show that triple-negative breast cancers (TNBCs) co-opt nociceptorneurons to suppress antitumor immunity and promote disease progression. Across orthotopic TNBC models, we foundthat primary tumors and tumor-draining lymph nodes were densely innervated by CGRP⁺ sensory fibers.

Tumor-derivedcues directly activated dorsal root ganglion neurons, increased calcium responsiveness, induced Ngfr and Atf3, andtriggered release of CGRP and substance P. Mechanistically, a tumor-derived proNGF-NGFR axis reprogrammednociceptors and promoted neuropeptide secretion. Soluble mediators from activated nociceptors suppressed CD8⁺ Tcell-mediated tumor-cell killing, whereas sensory-neuron silencing or ablation curtailed tumor growth and remodeled theimmune microenvironment toward dendritic-cell activation, myeloid reprogramming, and enhanced CD8⁺ T cell and NK-cell effector states.