{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:06:57Z","timestamp":1783980417095,"version":"3.55.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Natural Science Foundation of China funded project","award":["82405389"],"award-info":[{"award-number":["82405389"]}]},{"name":"Clinical Research Project of the National Medical Center, Longhua Hospital Shanghai University of Traditional Chinese Medicine","award":["GFB2401-1-3"],"award-info":[{"award-number":["GFB2401-1-3"]}]},{"name":"High-level Chinese Medicine Key Discipline Construction Project of National Administration of Traditional Chines Medicine","award":["zyyzdxk-2023068"],"award-info":[{"award-number":["zyyzdxk-2023068"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chin Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Targeting the neuro-immune microenvironment to suppress triple-negative breast cancer (TNBC) represents a critical strategy in tumor immunotherapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A syngeneic 4T1 orthotopic TNBC model in Balb\/c mice was employed. EA was applied at ST36 (Zusanli) using systematically optimized parameters (2\/15\u00a0Hz, 3\u00a0mA, 30\u00a0min, every other day). Multi-dimensional immunophenotyping by flow cytometry, immunofluorescence, and Western blot was performed across tumor, blood, and splenic compartments. Transcriptome sequencing coupled with KEGG\/GSEA pathway analysis was used to identify downstream signaling networks. The NGF\/Hippo\/YAP axis and adrenergic receptor subtype specificity were validated through pharmacological intervention in vitro, while EA synergy with \u03b1PD-L1 was assessed in a CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-depletion model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      ST36 stimulation at 3\u00a0mA preferentially suppressed TNBC tumor growth and augmented intratumoral immune infiltration, characterized by elevated CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, NK cells, and M1-polarized macrophages. EA significantly enhanced CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell effector capacity, upregulating perforin, granzyme B, CD69, and ZAP70 phosphorylation, and synergized with \u03b1PD-L1 in a CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-dependent manner. Mechanistically, EA activated c-Fos\n                      <jats:sup>+<\/jats:sup>\n                      \/ChAT\n                      <jats:sup>+<\/jats:sup>\n                      cholinergic neurons in the dorsal motor nucleus of the vagus (DMV) and reduced norepinephrine (NE) output in both circulation and tumors. Transcriptomic profiling identified NGF downregulation and Hippo pathway activation as central events. EA upregulated AMOT, driving YAP phosphorylation at Ser127, cytoplasmic sequestration of YAP, and suppression of downstream IL-6 secretion. In vitro, exogenous NGF suppressed YAP phosphorylation and promoted TNBC malignant behavior, effects fully reversed by the YAP inhibitor verteporfin. \u03b12-adrenergic receptor (\u03b12-AR) antagonism with yohimbine abrogated NE-induced NGF upregulation, pinpointing \u03b12-AR as the receptor subtype linking sympathetic signaling to the NGF\/Hippo axis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      EA at ST36 recalibrates neuro-sympathetic tone in TNBC by activating vagal cholinergic outflow, reducing NE-driven \u03b12-AR\/NGF\/Hippo signaling, and thereby relieving immunosuppression while amplifying CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cell-mediated cytotoxicity. These findings establish a neuro-immune mechanistic framework for EA-based adjuvant immunotherapy in TNBC.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13020-026-01445-6","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:21:24Z","timestamp":1783934484000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Electroacupuncture enhances anti-tumor immunity in TNBC by reducing NE release and blocking \u03b12-AR-mediated NGF\/Hippo signaling"],"prefix":"10.1186","volume":"21","author":[{"given":"Fei-Fei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Fang","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Yu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Ping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Nong","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Gan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"issue":"20","key":"1445_CR1","doi-asserted-by":"publisher","first-page":"2429","DOI":"10.1097\/CM9.0000000000003278","volume":"137","author":"K Sun","year":"2024","unstructured":"Sun K, Zhang B, Lei S, et al. Incidence, mortality, and disability-adjusted life years of female breast cancer in China, 2022. Chin Med J (Engl). 2024;137(20):2429\u201336.","journal-title":"Chin Med J (Engl)"},{"issue":"1","key":"1445_CR2","first-page":"17","volume":"73","author":"RL Siegel","year":"2023","unstructured":"Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17\u201348.","journal-title":"CA Cancer J Clin"},{"issue":"5","key":"1445_CR3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/oncolo\/oyaf052","volume":"30","author":"M Palleschi","year":"2025","unstructured":"Palleschi M, Virga A, Scarpi E, et al. Exploring the promoter regions of cancer predisposition genes in patients with triple-negative breast cancer reveals the presence of rare germline variants. Oncologist. 2025;30(5):52.","journal-title":"Oncologist"},{"issue":"24","key":"1445_CR4","doi-asserted-by":"publisher","first-page":"5249","DOI":"10.1158\/1078-0432.CCR-22-1110","volume":"28","author":"M Shah","year":"2022","unstructured":"Shah M, Osgood CL, Amatya AK, et al. FDA approval summary: pembrolizumab for neoadjuvant and adjuvant treatment of patients with high-risk early-stage triple-negative breast cancer. Clin Cancer Res. 2022;28(24):5249\u201353.","journal-title":"Clin Cancer Res"},{"key":"1445_CR5","doi-asserted-by":"publisher","first-page":"1561563","DOI":"10.3389\/fimmu.2025.1561563","volume":"16","author":"C Wang","year":"2025","unstructured":"Wang C, Zhao X, Wang D, et al. Analysis of prognostic factors and nomogram construction for postoperative survival of triple-negative breast cancer. Front Immunol. 2025;16:1561563.","journal-title":"Front Immunol"},{"key":"1445_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032969","author":"NS VAN DEN Ende","year":"2023","unstructured":"VAN DEN Ende NS, Nguyen AH, Jager A, et al. Triple-negative breast cancer and predictive markers of response to neoadjuvant chemotherapy: a systematic review. Int J Mol Sci. 2023. https:\/\/doi.org\/10.3390\/ijms24032969.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"1445_CR7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1158\/2326-6066.CIR-23-0076","volume":"12","author":"B Donati","year":"2024","unstructured":"Donati B, Reggiani F, Torricelli F, et al. Spatial distribution of immune cells drives resistance to neoadjuvant chemotherapy in triple-negative breast cancer. Cancer Immunol Res. 2024;12(1):120\u201334.","journal-title":"Cancer Immunol Res"},{"key":"1445_CR8","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010365","author":"Y Chen","year":"2025","unstructured":"Chen Y, Yang L, Huang Y, et al. Intratumoral microbiota predicts the response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer. J Immunother Cancer. 2025. https:\/\/doi.org\/10.1136\/jitc-2024-010365.","journal-title":"J Immunother Cancer"},{"key":"1445_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2023.103668","volume":"73","author":"F-I Dimitrakopoulos","year":"2024","unstructured":"Dimitrakopoulos F-I, Goussia A, Koliou G-A, et al. Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: a hellenic cooperative oncology group observational study (HE 10\/10) with concurrent investigation of significance of tumor infiltrating lymphocytes. The Breast. 2024;73:103668.","journal-title":"The Breast"},{"issue":"3","key":"1445_CR10","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1093\/qjmed\/hcad134","volume":"117","author":"F Liu","year":"2024","unstructured":"Liu F, Wang Y, Lyu K, et al. Acupuncture and its ability to restore and maintain immune homeostasis. QJM. 2024;117(3):167\u201376.","journal-title":"QJM"},{"key":"1445_CR11","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119259","volume":"272","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Yu Q, Zhang X, et al. Electroacupuncture regulates inflammatory cytokines by activating the vagus nerve to enhance antitumor immunity in mice with breast tumors. Life Sci. 2021;272:119259.","journal-title":"Life Sci"},{"issue":"1","key":"1445_CR12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1158\/2326-6066.CIR-23-0309","volume":"12","author":"Y Wang","year":"2024","unstructured":"Wang Y, Liu F, Du X, et al. Combination of anti-PD-1 and electroacupuncture induces a potent antitumor immune response in microsatellite-stable colorectal cancer. Cancer Immunol Res. 2024;12(1):26\u201335.","journal-title":"Cancer Immunol Res"},{"issue":"12","key":"1445_CR13","first-page":"1111","volume":"32","author":"D-W Yuan","year":"2024","unstructured":"Yuan D-W, Tang H-F, Wang H, et al. Effects of zusanli injection combined with abdominal acupoint application on gastrointestinal function recovery, immune function, and inflammatory status after laparoscopic surgery. Chin J Integr Gastroenterol. 2024;32(12):1111\u20135.","journal-title":"Chin J Integr Gastroenterol"},{"key":"1445_CR14","unstructured":"Wang M. Effects of acupuncture on tumor immune cells in tumor-bearing mice. Anhui Agricultural University, 2024."},{"key":"1445_CR15","unstructured":"Wu Y-J. Study on the effects of electroacupuncture at \u201cTianshu\u201d and \u201cZusanli\u201d on ROR\u03b3t\/STAT3 protein levels and immune dysregulation in UC rats. [D]. Liaoning University of Traditional Chinese Medicine, 2021."},{"issue":"7882","key":"1445_CR16","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41586-021-04001-4","volume":"598","author":"S Liu","year":"2021","unstructured":"Liu S, Wang Z, Su Y, et al. A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis. Nature. 2021;598(7882):641\u20135.","journal-title":"Nature"},{"key":"1445_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.07.015","author":"S Liu","year":"2020","unstructured":"Liu S, Wang Z-F, Su Y-S, et al. Somatotopic organization and intensity dependence in driving distinct NPY-expressing sympathetic pathways by electroacupuncture. Neuron. 2020. https:\/\/doi.org\/10.1016\/j.neuron.2020.07.015.","journal-title":"Neuron"},{"issue":"1","key":"1445_CR18","doi-asserted-by":"publisher","first-page":"2502354","DOI":"10.1080\/2162402X.2025.2502354","volume":"14","author":"C Abrate","year":"2025","unstructured":"Abrate C, Canale FP, Bossio SN, et al. CD8+ T cells in breast cancer tumors and draining lymph nodes: PD-1 levels, effector functions and prognostic relevance. Oncoimmunology. 2025;14(1):2502354.","journal-title":"Oncoimmunology"},{"issue":"3","key":"1445_CR19","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/nm.3479","volume":"20","author":"R Torres-Rosas","year":"2014","unstructured":"Torres-Rosas R, Yehia G, PE\u00f1A G, et al. Dopamine mediates vagal modulation of the immune system by electroacupuncture. Nat Med. 2014;20(3):291\u20135.","journal-title":"Nat Med"},{"issue":"11","key":"1445_CR20","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1017\/S109285290002191X","volume":"5","author":"MS George","year":"2000","unstructured":"George MS, Nahas Z, Bohning DE, et al. Vagus nerve stimulation: a new form of therapeutic brain stimulation. CNS Spectr. 2000;5(11):43\u201352.","journal-title":"CNS Spectr"},{"issue":"6","key":"1445_CR21","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s10286-024-01065-w","volume":"34","author":"CW Austelle","year":"2024","unstructured":"Austelle CW, Cox SS, Wills KE, et al. Vagus nerve stimulation (VNS): recent advances and future directions. Clin Auton Res. 2024;34(6):529\u201347.","journal-title":"Clin Auton Res"},{"key":"1445_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/cimb47020122","author":"Z Chen","year":"2025","unstructured":"Chen Z, Liu K. Mechanism and applications of vagus nerve stimulation. Curr Issues Mol Biol. 2025. https:\/\/doi.org\/10.3390\/cimb47020122.","journal-title":"Curr Issues Mol Biol"},{"issue":"1","key":"1445_CR23","first-page":"59","volume":"23","author":"RT Jackson","year":"1985","unstructured":"Jackson RT, Steele RW. The inhibition of norepinephrine release in nasal mucosa by acetylcholine. Rhinology. 1985;23(1):59\u201364.","journal-title":"Rhinology"},{"key":"1445_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.838484","volume":"13","author":"A KN\u00f6RCK","year":"2022","unstructured":"KN\u00f6RCK A, SCH\u00e4FER G, Alansary D, et al. Cytotoxic efficiency of human CD8+ T cell memory subtypes. Front Immunol. 2022;13:838484.","journal-title":"Front Immunol"},{"issue":"7","key":"1445_CR25","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1016\/j.annonc.2025.03.011","volume":"36","author":"R Bartolini","year":"2025","unstructured":"Bartolini R, Trueb L, Daoudlarian D, et al. Enrichment of CD7+CXCR3+ CAR T-cells in infusion products is associated with durable remission in relapsed or refractory diffuse large B-cell lymphoma. Ann Oncol. 2025;36(7):749\u201361.","journal-title":"Ann Oncol"},{"issue":"10","key":"1445_CR26","doi-asserted-by":"publisher","first-page":"e002758","DOI":"10.1136\/jitc-2021-002758","volume":"9","author":"W-L Yan","year":"2021","unstructured":"Yan W-L, Wu C-C, Shen K-Y, et al. Activation of GM-CSF and TLR2 signaling synergistically enhances antigen-specific antitumor immunity and modulates the tumor microenvironment. J Immunother Cancer. 2021;9(10):e002758.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"1445_CR27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13045-024-01649-z","volume":"17","author":"NK Heater","year":"2024","unstructured":"Heater NK, Warrior S, Lu J. Current and future immunotherapy for breast cancer. J Hematol Oncol. 2024;17(1):131.","journal-title":"J Hematol Oncol"},{"issue":"8","key":"1445_CR28","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1158\/2326-6066.CIR-24-0937","volume":"13","author":"M Desbois","year":"2025","unstructured":"Desbois M, Giffon T, Yakkundi P, et al. IGM-7354, an immunocytokine with IL-15 fused to an anti-PD-L1 IgM, induces NK and CD8+ T cell-mediated cytotoxicity of PD-L1 positive tumor cells. Cancer Immunol Res. 2025;13(8):1172\u201389.","journal-title":"Cancer Immunol Res"},{"issue":"2","key":"1445_CR29","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/s41401-024-01381-x","volume":"46","author":"F-L Li","year":"2025","unstructured":"Li F-L, Gu L-H, Tong Y-L, et al. INHBA promotes tumor growth and induces resistance to PD-L1 blockade by suppressing IFN-\u03b3 signaling. Acta Pharmacol Sin. 2025;46(2):448\u201361.","journal-title":"Acta Pharmacol Sin"},{"key":"1445_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109402","volume":"114","author":"L Assy","year":"2023","unstructured":"Assy L, Khalil SM, Attia M, et al. IL-12 conditioning of peripheral blood mononuclear cells from breast cancer patients promotes the zoledronate-induced expansion of \u03b3\u03b4 T cells in vitro and enhances their cytotoxic activity and cytokine production. Int Immunopharmacol. 2023;114:109402.","journal-title":"Int Immunopharmacol"},{"issue":"8059","key":"1445_CR31","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1038\/s41586-025-08591-1","volume":"640","author":"X Zhi","year":"2025","unstructured":"Zhi X, Wu F, Qian J, et al. Nociceptive neurons promote gastric tumour progression via a CGRP-RAMP1 axis. Nature. 2025;640(8059):802\u201310.","journal-title":"Nature"},{"key":"1445_CR32","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011609","author":"E Repasky","year":"2025","unstructured":"Repasky E, Mohammadpour H. Targeting nerve growth factor: an Achilles\u2019 heel for tumors? J Immunother Cancer. 2025. https:\/\/doi.org\/10.1136\/jitc-2025-011609.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"1445_CR33","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41419-025-07746-2","volume":"16","author":"Z Liu","year":"2025","unstructured":"Liu Z, Zhang C, Gai Y, et al. VCPIP1 facilitates pancreatic adenocarcinoma progression via Hippo\/YAP signaling. Cell Death Dis. 2025;16(1):422.","journal-title":"Cell Death Dis"},{"key":"1445_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217846","author":"Z Xiang","year":"2025","unstructured":"Xiang Z, Li J, Xu Y, et al. Cell differentiation-related signaling pathways in hepatocellular carcinoma metastasis. Cancer Lett. 2025. https:\/\/doi.org\/10.1016\/j.canlet.2025.217846.","journal-title":"Cancer Lett"},{"issue":"16","key":"1445_CR35","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/s41388-023-02677-8","volume":"42","author":"P Amirifar","year":"2023","unstructured":"Amirifar P, Kissil J. The role of Motin family proteins in tumorigenesis-an update. Oncogene. 2023;42(16):1265\u201371.","journal-title":"Oncogene"},{"issue":"6","key":"1445_CR36","doi-asserted-by":"publisher","first-page":"3647","DOI":"10.1007\/s11010-024-05194-8","volume":"480","author":"M Tang","year":"2025","unstructured":"Tang M, Song K, Xie D, et al. PSAT1 promotes the progression of colorectal cancer by regulating Hippo-YAP\/TAZ-ID1 axis via AMOT. Mol Cell Biochem. 2025;480(6):3647\u201368.","journal-title":"Mol Cell Biochem"},{"issue":"1","key":"1445_CR37","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41419-022-04516-2","volume":"13","author":"Q Tian","year":"2022","unstructured":"Tian Q, Gao H, Zhou Y, et al. RICH1 inhibits breast cancer stem cell traits through activating kinases cascade of Hippo signaling by competing with Merlin for binding to Amot-p80. Cell Death Dis. 2022;13(1):71.","journal-title":"Cell Death Dis"},{"issue":"1","key":"1445_CR38","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13058-025-02028-3","volume":"27","author":"N Deng","year":"2025","unstructured":"Deng N, Kang W, Du J, et al. Microtubule associated serine\/threonine kinase-3 inhibits the malignant phenotype of breast cancer by promoting phosphorylation-mediated ubiquitination degradation of yes-associated protein. Breast Cancer Res. 2025;27(1):63.","journal-title":"Breast Cancer Res"},{"issue":"2","key":"1445_CR39","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.gendis.2023.01.017","volume":"11","author":"F Sadri","year":"2024","unstructured":"Sadri F, Hosseini SF, Rezaei Z, et al. Hippo-YAP\/TAZ signaling in breast cancer: reciprocal regulation of microRNAs and implications in precision medicine. Genes Dis. 2024;11(2):760\u201371.","journal-title":"Genes Dis"},{"key":"1445_CR40","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.688794","volume":"11","author":"L Wang","year":"2021","unstructured":"Wang L, Li J, Wang R, et al. NGF signaling interacts with the Hippo\/YAP pathway to regulate cervical cancer progression. Front Oncol. 2021;11:688794.","journal-title":"Front Oncol"},{"issue":"1","key":"1445_CR41","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1158\/2159-8290.CD-24-0287","volume":"15","author":"H Kobayashi","year":"2025","unstructured":"Kobayashi H, Iida T, Ochiai Y, et al. Neuro-mesenchymal interaction mediated by a \u03b22-adrenergic nerve growth factor feedforward loop promotes colorectal cancer progression. Cancer Discov. 2025;15(1):202\u201326.","journal-title":"Cancer Discov"},{"key":"1445_CR42","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxaf009","author":"R Hasebe","year":"2025","unstructured":"Hasebe R, Tanaka H, Yamasaki T, et al. Neural signaling in immunology: the gateway reflex. Int Immunol. 2025. https:\/\/doi.org\/10.1093\/intimm\/dxaf009.","journal-title":"Int Immunol"},{"key":"1445_CR43","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.151087","volume":"741","author":"H-J Park","year":"2024","unstructured":"Park H-J, Lee S-C, Park S-H. Norepinephrine stimulates M2 macrophage polarization via \u03b22-adrenergic receptor-mediated IL-6 production in breast cancer cells. Biochem Biophys Res Commun. 2024;741:151087.","journal-title":"Biochem Biophys Res Commun"},{"issue":"03","key":"1445_CR44","first-page":"1240","volume":"24","author":"M-J Li","year":"2022","unstructured":"Li M-J, Zhang J-Q, Jiang F, et al. Visual analysis of research on zusanli acupoint based on CiteSpace. World Sci Technol Mod Tradit Chin Med. 2022;24(03):1240\u201352.","journal-title":"World Sci Technol Mod Tradit Chin Med"},{"issue":"12","key":"1445_CR45","first-page":"2521","volume":"35","author":"J-Y Chen","year":"2020","unstructured":"Chen J-Y, Tang H-T, Wang H, et al. Exploring Zusanli. Chin J Tradit Med. 2020;35(12):2521\u20134.","journal-title":"Chin J Tradit Med"},{"issue":"32","key":"1445_CR46","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202402856","volume":"11","author":"L Yang","year":"2024","unstructured":"Yang L, Zhou Y, Huang Z, et al. Electroacupuncture promotes liver regeneration by activating DMV acetylcholinergic neurons-vagus-macrophage axis in 70% partial hepatectomy of mice. Adv Sci (Weinh). 2024;11(32):e2402856.","journal-title":"Adv Sci (Weinh)"},{"issue":"9","key":"1445_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19386","volume":"9","author":"F Guo","year":"2023","unstructured":"Guo F, Han R, Sun L, et al. Effect of transcutaneous electrical acupoint stimulation on postoperative cognitive function in older patients with lung cancer: a randomized, double-blind, placebo-controlled trial. Heliyon. 2023;9(9):e19386.","journal-title":"Heliyon"},{"issue":"1","key":"1445_CR48","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1186\/s12955-023-02135-9","volume":"21","author":"X Chang","year":"2023","unstructured":"Chang X, Zhu Y, Zhao W, et al. Electro-acupuncture for health-related quality of life and symptoms in patients with gastric cancer undergoing adjuvant chemotherapy (EAGER): a protocol for a multicenter randomized controlled trial. Health Qual Life Outcomes. 2023;21(1):70.","journal-title":"Health Qual Life Outcomes"},{"issue":"12","key":"1445_CR49","first-page":"3118","volume":"26","author":"Y-F Song","year":"2024","unstructured":"Song Y-F, Zhang X-M, Jiang S-Y, et al. Mechanism of acupuncture stimulation at Zusanli and Ganshu points in inhibiting liver metastasis of colon cancer cells in nude mice: a study on gut microbiota. World Sci Technol Mod Tradit Chin Med. 2024;26(12):3118\u201326.","journal-title":"World Sci Technol Mod Tradit Chin Med"},{"issue":"2","key":"1445_CR50","first-page":"394","volume":"13","author":"Y-F Song","year":"2023","unstructured":"Song Y-F, Zhou J-Y, Zhuang Y, et al. Moxibustion attenuates liver metastasis of colorectal cancer by regulating gut microbial dysbiosis. Am J Cancer Res. 2023;13(2):394\u2013407.","journal-title":"Am J Cancer Res"},{"issue":"1","key":"1445_CR51","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13020-025-01134-w","volume":"20","author":"W Shen","year":"2025","unstructured":"Shen W, Hu D, Gong C, et al. Grain-sized moxibustion activates dendritic cells to enhance the antitumor immunity of cancer vaccines. Chin Med. 2025;20(1):73.","journal-title":"Chin Med"},{"issue":"10","key":"1445_CR52","first-page":"866","volume":"47","author":"X-Y Sun","year":"2022","unstructured":"Sun X-Y, Wang H-Y, Zhang Z-Y, et al. Mechanism study of electroacupuncture at Zusanli in delaying colitis-associated carcinogenesis. Acupunct Res. 2022;47(10):866\u201371.","journal-title":"Acupunct Res"},{"issue":"6","key":"1445_CR53","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1007\/s40122-023-00549-3","volume":"12","author":"Q-Y Li","year":"2023","unstructured":"Li Q-Y, Yang W-X, Yao L-Q, et al. Exploring the rules of related parameters in transcutaneous electrical nerve stimulation for cancer pain based on data mining. Pain Ther. 2023;12(6):1355\u201374.","journal-title":"Pain Ther"},{"issue":"21","key":"1445_CR54","first-page":"3039","volume":"17","author":"H-Y Wang","year":"2022","unstructured":"Wang H-Y, Zhang Z-Y, Zhang X-N, et al. Preliminary observation on the time window and immunological mechanism of electroacupuncture\u2019s antitumor effect in breast cancer mice. World J Tradit Chin Med. 2022;17(21):3039\u201344.","journal-title":"World J Tradit Chin Med"},{"key":"1445_CR55","unstructured":"PEI L-J, Mechanism of antitumor effect of electroacupuncture at zusanli based on the \u201cNeuro-Immune\u201d network [D]. Shanghai University of Traditional Chinese Medicine, 2021."},{"issue":"1","key":"1445_CR56","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s13046-023-02836-5","volume":"42","author":"J Pan","year":"2023","unstructured":"Pan J, Zhang L, Wang X, et al. Chronic stress induces pulmonary epithelial cells to produce acetylcholine that remodels lung pre-metastatic niche of breast cancer by enhancing NETosis. J Exp Clin Cancer Res. 2023;42(1):255.","journal-title":"J Exp Clin Cancer Res"},{"issue":"10","key":"1445_CR57","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1158\/0008-5472.CAN-19-2689","volume":"80","author":"M-W Yang","year":"2020","unstructured":"Yang M-W, Tao L-Y, Jiang Y-S, et al. Perineural invasion reprogramS the immune microenvironment through cholinergic signaling in pancreatic ductal adenocarcinoma. Cancer Res. 2020;80(10):1991\u20132003.","journal-title":"Cancer Res"},{"issue":"13","key":"1445_CR58","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr9916","volume":"11","author":"H Wang","year":"2025","unstructured":"Wang H, Ortega HK, Kelly EB, et al. Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making. Sci Adv. 2025;11(13):eadr9916.","journal-title":"Sci Adv"},{"issue":"11","key":"1445_CR59","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1007\/s00262-014-1617-9","volume":"63","author":"JWL Eng","year":"2014","unstructured":"Eng JWL, Kokolus KM, Reed CB, et al. A nervous tumor microenvironment: the impact of adrenergic stress on cancer cells, immunosuppression, and immunotherapeutic response. Cancer Immunol Immunother. 2014;63(11):1115\u201328.","journal-title":"Cancer Immunol Immunother"},{"issue":"4","key":"1445_CR60","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1002\/jcp.30707","volume":"237","author":"D Silva","year":"2022","unstructured":"Silva D, Quintas C, GON\u00e7ALVES J, et al. Contribution of adrenergic mechanisms for the stress-induced breast cancer carcinogenesis. J Cell Physiol. 2022;237(4):2107\u201327.","journal-title":"J Cell Physiol"},{"issue":"1","key":"1445_CR61","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1186\/s12885-022-09330-9","volume":"22","author":"X Wang","year":"2022","unstructured":"Wang X, Wang Y, Xie F, et al. Norepinephrine promotes glioma cell migration through up-regulating the expression of Twist1. BMC Cancer. 2022;22(1):213.","journal-title":"BMC Cancer"},{"issue":"7","key":"1445_CR62","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/s41416-022-02132-7","volume":"128","author":"Q Geng","year":"2023","unstructured":"Geng Q, Li L, Shen Z, et al. Norepinephrine inhibits CD8+ T-cell infiltration and function, inducing anti-PD-1 mAb resistance in lung adenocarcinoma. Br J Cancer. 2023;128(7):1223\u201335.","journal-title":"Br J Cancer"},{"issue":"2","key":"1445_CR63","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/0014-2999(78)90327-8","volume":"48","author":"L Beani","year":"1978","unstructured":"Beani L, Bianchi C, Giacomelli A, et al. Noradrenaline inhibition of acetylcholine release from guinea-pig brain. Eur J Pharmacol. 1978;48(2):179\u201393.","journal-title":"Eur J Pharmacol"},{"issue":"6058","key":"1445_CR64","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1038\/320172a0","volume":"320","author":"MF Bear","year":"1986","unstructured":"Bear MF, Singer W. Modulation of visual cortical plasticity by acetylcholine and noradrenaline. Nature. 1986;320(6058):172\u20136.","journal-title":"Nature"},{"key":"1445_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.04.030","author":"WD Green","year":"2025","unstructured":"Green WD, Gomez A, Plotkin AL, et al. Enhancer-driven gene regulatory networks reveal transcription factors governing T cell adaptation and differentiation in the tumor microenvironment. Immunity. 2025. https:\/\/doi.org\/10.1016\/j.immuni.2025.04.030.","journal-title":"Immunity"},{"issue":"6","key":"1445_CR66","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1111\/cas.70055","volume":"116","author":"R Koyama-Nasu","year":"2025","unstructured":"Koyama-Nasu R, Wang Y, Miyano H, et al. Differentiation of cytotoxic CD8+ T cell subsets under tumor progression: Can CD69 be a new therapeutic target? Cancer Sci. 2025;116(6):1500\u20137.","journal-title":"Cancer Sci"},{"issue":"6","key":"1445_CR67","doi-asserted-by":"publisher","first-page":"2873","DOI":"10.4049\/jimmunol.1400858","volume":"193","author":"I Schim Van Der Loeff","year":"2014","unstructured":"Schim Van Der Loeff I, Hsu L-Y, Saini M, et al. Zap70 is essential for long-term survival of naive CD8 T cells. J Immunol. 2014;193(6):2873\u201380.","journal-title":"J Immunol"},{"key":"1445_CR68","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008334","author":"M Tone","year":"2024","unstructured":"Tone M, Iwahori K, Hirata M, et al. Tetracyclines enhance antitumor T-cell immunity via the Zap70 signaling pathway. J Immunother Cancer. 2024. https:\/\/doi.org\/10.1136\/jitc-2023-008334.","journal-title":"J Immunother Cancer"},{"key":"1445_CR69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1569042","volume":"16","author":"P Huang","year":"2025","unstructured":"Huang P, Zhao M, Xia J, et al. IL-6 is a prognostic biomarker in patients with advanced esophageal squamous cell carcinoma received with PD-1 inhibitors. Front Immunol. 2025;16:1569042.","journal-title":"Front Immunol"},{"issue":"1","key":"1445_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2022.100878","volume":"4","author":"MA Huseni","year":"2023","unstructured":"Huseni MA, Wang L, Klementowicz JE, et al. CD8+ T cell-intrinsic IL-6 signaling promotes resistance to anti-PD-L1 immunotherapy. Cell Rep Med. 2023;4(1):100878.","journal-title":"Cell Rep Med"},{"issue":"26","key":"1445_CR71","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202306348","volume":"11","author":"M Tang","year":"2024","unstructured":"Tang M, Xu M, Wang J, et al. Brain metastasis from EGFR-mutated non-small cell lung cancer: secretion of IL11 from astrocytes up-regulates PDL1 and promotes immune escape. Adv Sci. 2024;11(26):e2306348.","journal-title":"Adv Sci"},{"issue":"15","key":"1445_CR72","doi-asserted-by":"publisher","first-page":"2778","DOI":"10.1038\/s41388-018-0609-1","volume":"38","author":"X Yang","year":"2019","unstructured":"Yang X, Shen H, Buckley B, et al. NTRK1 is a positive regulator of YAP oncogenic function. Oncogene. 2019;38(15):2778\u201387.","journal-title":"Oncogene"},{"key":"1445_CR73","doi-asserted-by":"publisher","DOI":"10.3390\/biom11070936","author":"Y Wu","year":"2021","unstructured":"Wu Y, Zeng L, Zhao S. Ligands of adrenergic receptors: a structural point of view. Biomolecules. 2021. https:\/\/doi.org\/10.3390\/biom11070936.","journal-title":"Biomolecules"}],"container-title":["Chinese Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-026-01445-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13020-026-01445-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13020-026-01445-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:02:20Z","timestamp":1783980140000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13020-026-01445-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1445"],"URL":"https:\/\/doi.org\/10.1186\/s13020-026-01445-6","relation":{},"ISSN":["1749-8546"],"issn-type":[{"value":"1749-8546","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"assertion":[{"value":"14 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"DeclarationsDeclarations"}},{"value":"The study protocol was approved by the Animal Ethics Committee of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Ethics No.: LHERAW-25053). Clinical trial number: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"186"}}