{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["650(8103)"],"submitter":["Wei HK"],"pubmed_abstract":["Body-brain communication has emerged as a key regulator of tissue homeostasis<sup>1-5</sup>. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes<sup>6-8</sup>. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour-brain communication influences cancer immunity. Here we identify a tumour-brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain. Mechanistically, Npy2r-expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β<sub>2</sub> adrenergic signalling in alveolar macrophages. Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer. Collectively, these results reveal a bidirectional tumour-brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour-brain circuit may provide new treatments for visceral organ cancers."],"journal":["Nature"],"pagination":["1007-1016"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12935554"],"repository":["biostudies-literature"],"pubmed_title":["Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis."],"pmcid":["PMC12935554"],"pubmed_authors":["Ichise H","Chang RB","Germain RN","Wang RL","Jin C","Zeng X","Wang Y","Wei HK","Hu B","Li L","Yu CD"],"additional_accession":[]},"is_claimable":false,"name":"Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis.","description":"Body-brain communication has emerged as a key regulator of tissue homeostasis<sup>1-5</sup>. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes<sup>6-8</sup>. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour-brain communication influences cancer immunity. Here we identify a tumour-brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain. Mechanistically, Npy2r-expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β<sub>2</sub> adrenergic signalling in alveolar macrophages. Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer. Collectively, these results reveal a bidirectional tumour-brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour-brain circuit may provide new treatments for visceral organ cancers.","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Feb","modification":"2026-07-10T03:22:12.803Z","creation":"2026-07-10T03:16:11.9Z"},"accession":"S-EPMC12935554","cross_references":{"pubmed":["41639447"],"doi":["10.1038/s41586-025-10028-8"]}}