{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336080/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336080"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Nociceptor neurons suppress antitumor immunity in breast cancer","description":"Peripheral nerves are emerging regulators of the tumor microenvironment, but how sensory innervation shapes breastcancer immunity remains poorly defined. 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. Subset-specific analysis revealed nonredundant sensory control of immune states, with MrgD⁺neurons selectively shaping macrophage-centered programs. Finally, blockade of CGRP signaling through RAMP1 reduced tumor growth and markedly enhanced PD-1 blockade, nearly eliminating primary tumor burden and lungmetastasis in vivo. T cell-specific Ramp1 deletion similarly restrained tumor growth, and RAMP1⁺ CD8⁺ T cells in humanTNBC displayed an exhaustion-associated phenotype. Together, these findings define a tumor-promoting proNGF-nociceptor-CGRP-RAMP1 axis and identify neuroimmune signaling as a therapeuticall","dates":{"publication":"2026/08/22"},"accession":"GSE336080","cross_references":{"GSM":["GSM9826724","GSM9826746","GSM9826745","GSM9826723","GSM9826748","GSM9826726","GSM9826747","GSM9826725","GSM9826742","GSM9826741","GSM9826722","GSM9826744","GSM9826743","GSM9826728","GSM9826727","GSM9826749","GSM9826729","GSM9826740","GSM9826735","GSM9826756","GSM9826734","GSM9826737","GSM9826736","GSM9826753","GSM9826731","GSM9826752","GSM9826730","GSM9826755","GSM9826733","GSM9826732","GSM9826754","GSM9826739","GSM9826738","GSM9826751","GSM9826750"],"GPL":["19057"],"GSE":["336080"],"taxon":["Mus musculus"]}}