de Visser KE, Joyce JA. The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell. 2023;41:374–403.
Google Scholar
Lu J, Zhang X, Su K, Luo H, Liu C, Yang Y, et al. Olanzapine suppresses mPFC activity-norepinephrine releasing to alleviate CLOCK-enhanced cancer stemness under chronic stress. Cell Commun Signal. 2024;22:375.
Google Scholar
Liu Z, Lei M, Bai Y. Chronic stress mediates inflammatory cytokines alterations and its role in tumorigenesis. J Inflamm Res. 2025;18:1067–90.
Google Scholar
Gysler SM, Drapkin R. Tumor innervation: peripheral nerves take control of the tumor microenvironment. J Clin Investig. 2021;131:e147276.
Google Scholar
Zeng Y, Hu CH, Li YZ, Zhou JS, Wang SX, Liu MD, et al. Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer. Nat Med. 2024;30:1680–8.
Google Scholar
He XY, Gao Y, Ng D, Michalopoulou E, George S, Adrover JM, et al. Chronic stress increases metastasis via neutrophil mediated changes to the microenvironment. Cancer Cell. 2024;42:474–86.e12.
Google Scholar
Le CP, Nowell CJ, Kim-Fuchs C, Botteri E, Hiller JG, Ismail H, et al. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun. 2016;7:10634.
Google Scholar
Zhang F, Xia Y, Su J, Quan F, Zhou H, Li Q, et al. Neutrophil diversity and function in health and disease. Signal Transduct Target Ther. 2024;9:343.
Google Scholar
Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.
Google Scholar
Yang S, Wang M, Hua Y, Li J, Zheng H, Cui M, et al. Advanced insights on tumor-associated macrophages revealed by single-cell RNA sequencing: the intratumor heterogeneity, functional phenotypes, and cellular interactions. Cancer Lett. 2024;584:216610.
Google Scholar
Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med. 2015;21:938–45.
Google Scholar
Mowery YM, Luke JJ. NETosis impact on tumor biology, radiation, and systemic therapy resistance. Clin Cancer Res. 2024;30:3965–7.
Google Scholar
Ning Y, Chen Y, Tian T, Gao X, Liu X, Wang J, et al. S100A7 orchestrates neutrophil chemotaxis and drives neutrophil extracellular traps (NETs) formation to facilitate lymph node metastasis in cervical cancer patients. Cancer Lett. 2024;605:217288.
Google Scholar
Xu L, Kong Y, Li K, Li J, Xu F, Xu Y, et al. Neutrophil extracellular traps promote growth of lung adenocarcinoma by mediating the stability of m6A-mediated SLC2A3 mRNA induced ferroptosis resistance and CD8(+) T cell inhibition. C. lin Transl Med. 2025;15:e70192.
Google Scholar
He G, Li Y, Deng H, Zuo H. Advances in the study of cholinergic circuits in the central nervous system. Ann Clin Transl Neurol. 2023;10:2179–91.
Google Scholar
Tibensky M, Mravec B. Role of the parasympathetic nervous system in cancer initiation and progression. Clin Transl Oncol. 2021;23:669–81.
Google Scholar
Zhao CM, Hayakawa Y, Kodama Y, Muthupalani S, Westphalen CB, Andersen GT, et al. Denervation suppresses gastric tumorigenesis. Sci Transl Med. 2014;6:250ra115.
Google Scholar
Wang L, Xu J, Xia Y, Yin K, Li Z, Li B, et al. Muscarinic acetylcholine receptor 3 mediates vagus nerve-induced gastric cancer. Oncogenesis. 2018;7:88.
Google Scholar
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209–49.
Google Scholar
Seo WJ, Lee S, Jang YJ, Choi SI, Kim JH. Lymphatic invasion as the solitary risk factor for extraperigastric lymph node metastasis in early gastric cancer. Surgery. 2025;181(May):109157.
Google Scholar
Yan J, Chen Y, Luo M, Hu X, Li H, Liu Q, et al. Chronic stress in solid tumor development: from mechanisms to interventions. J Biomed Sci. 2023;30:8.
Google Scholar
Yu X, Li C, Wang Z, Xu Y, Shao S, Shao F, et al. Neutrophils in cancer: dual roles through intercellular interactions. Oncogene. 2024;43:1163–77.
Google Scholar
Najmeh S, Cools-Lartigue J, Giannias B, Spicer J, Ferri LE. Simplified human Neutrophil Extracellular Traps (NETs) Isolation and Handling. J Vis Exp. 2015;98:52687.
Cao Q, Zhao M, Su Y, Liu S, Lin Y, Da H, et al. Chronic stress dampens lactobacillus johnsonii-mediated tumor suppression to enhance colorectal cancer progression. Cancer Res. 2024;84:771–84.
Google Scholar
Andersen BL, DeRubeis RJ, Berman BS, Gruman J, Champion VL, Massie MJ, et al. Screening, assessment, and care of anxiety and depressive symptoms in adults with cancer: an American Society of Clinical Oncology guideline adaptation. J Clin Oncol. 2014;32:1605–19.
Google Scholar
Yang LY, Luo Q, Lu L, Zhu WW, Sun HT, Wei R, et al. Increased neutrophil extracellular traps promote metastasis potential of hepatocellular carcinoma via provoking tumorous inflammatory response. J Hematol Oncol. 2020;13:3.
Google Scholar
Huh HD, Sub Y, Oh J, Kim YE, Lee JY, Kim HR, et al. Reprogramming anchorage dependency by adherent to-suspension transition promotes metastatic dissemination. Mol Cancer. 2023;22(Aug):135.
Google Scholar
Dupont S, Morsut L, Aragona M, Enzo E, Giulitti S, Cordenonsi M, et al. Role of YAP/TAZ in mechanotransduction. Nature. 2011;474:179–83.
Google Scholar
Guo W, Gong Q, Zong X, Wu D, Li Y, Xiao H, et al. GPR109A controls neutrophil extracellular traps formation and improve early sepsis by regulating ROS/PAD4/Cit-H3 signal axis. Exp Hematol Oncol. 2023;12:15.
Google Scholar
Fukai T, Ushio-Fukai M. Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cells. 2020;9:1849.
Google Scholar
Damascena HL, Silveira WAA, Castro MS, Fontes W. Neutrophil activated by the famous and potent PMA (Phorbol Myristate Acetate). Cells. 2022;11:2889.
Google Scholar
Barman B, Kushwaha A, Thakur MK. Muscarinic acetylcholine receptors-mediated activation of PKC restores the hippocampal immediate early gene expression and CREB phosphorylation in scopolamine-induced amnesic mice. Mol Neurobiol. 2022;59:5722–33.
Google Scholar
Wang C, Zheng X, Zhang J, Jiang X, Wang J, Li Y, et al. CD300ld on neutrophils is required for tumour-driven immune suppression. Nature. 2023;621:830–9.
Google Scholar
Chen Y, Ouyang Y, Li Z, Wang X, Ma J. S100A8 and S100A9 in cancer. Biochim Biophys Acta Rev Cancer. 2023;1878:188891.
Google Scholar
Lin S, Wang L, Han C, Dai Y, Li C, Liu Y, et al. Targeting HTR2B suppresses nonfunctioning pituitary adenoma growth and sensitizes cabergoline treatment via inhibiting Gαq/PLC/PKCγ/STAT3 axis. Neuro Oncol. 2024;26:2010–26.
Google Scholar
Weihrauch T, Limberg MM, Gray N, Schmelz M, Raap U. Neurotrophins: neuroimmune interactions in human atopic diseases. Int J Mol Sci. 2023;24:6105.
Google Scholar
Mahmoud AI, O’Meara CC, Gemberling M, Zhao L, Bryant DM, Zheng R, et al. Nerves regulate cardiomyocyte proliferation and heart regeneration. Dev Cell. 2015;34:387–99.
Google Scholar
Kannan Y, Ushio H, Koyama H, Okada M, Oikawa M, Yoshihara T, et al. 2.5S nerve growth factor enhances survival, phagocytosis, and superoxide production of murine neutrophils. Blood. 1991;77:1320–5.
Google Scholar
Puntambekar P, Mukherjea D, Jajoo S, Ramkumar V. Essential role of Rac1/NADPH oxidase in nerve growth factor induction of TRPV1 expression. J Neurochem. 2005;95:1689–703.
Google Scholar
Pritzl SL, Vierkant RA, Ruddy KJ, Stan DL, Larson NL, Olson JE, et al. Trajectory of global mental health and global physical health in breast cancer survivorship. J Natl Compr Canc Netw. 2025;23:141–6.
Google Scholar
Zhang H, Yang Y, Cao Y, Guan J. Effects of chronic stress on cancer development and the therapeutic prospects of adrenergic signaling regulation. Biomed Pharmacother. 2024;175:116609.
Google Scholar
Momčilović S, Milošević M, Kočović DM, Marković D, Zdravković D, Vignjević Petrinović S. Macrophages at the crossroads of chronic stress and cancer. Int J Mol Sci. 2025;26:6838.
Google Scholar
Zhang L, Pan J, Wang M, Yang J, Zhu S, Li L, et al. Chronic stress-induced and tumor derived SP1+ exosomes polarizing IL-1β+ neutrophils to increase lung metastasis of breast cancer. Adv Sci. 2025;12:e2310266.
Google Scholar
Chen D, Xu J, Zhao Y, Han B, Zhong R. Prognostic value of pretreatment procalcitonin and neutrophil-lymphocyte ratio in extensive-stage small-cell lung cancer. Cancer Biol Ther. 2024;25:2331273.
Google Scholar
Rocco A, Sgamato C, Pelizzaro F, Simeon V, Coccoli P, Compare D, et al. Systemic inflammatory response markers improve the discrimination for prognostic model in hepatocellular carcinoma. Hepatol Int. 2025;19:915–28.
Google Scholar
Su H, Liao D, Huang C, Liu Q, Yu L. Low Serum cholinesterase levels predict poor prognosis in patients with ovarian cancer. Int J Gen Med. 2025;18:1023–33.
Google Scholar
Ran H, Ma J, Cai L, Zhou H, Yuan Z, Chen Y, et al. Serum cholinesterase may independently predict prognosis in non-small-cell lung cancer. BMC Cancer. 2022;22:93.
Google Scholar
Bi Y, Zhang J, Zeng D, Chen L, Ye W, Yang Q, et al. Cholinesterase is associated with prognosis and response to chemotherapy in advanced gastric cancer. Pathol Oncol Res. 2021;27:580800.
Google Scholar
Wang Y, Wang X, Wang K, Qi J, Zhang Y, Wang X, et al. Chronic stress accelerates glioblastoma progression via DRD2/ERK/β-catenin axis and Dopamine/ERK/TH positive feedback loop. J Exp Clin Cancer Res. 2023;42:161.
Google Scholar
Zheng Y, Wang N, Wang S, Zhang J, Yang B, Wang Z. Chronic psychological stress promotes breast cancer pre-metastatic niche formation by mobilizing splenic MDSCs via TAM/CXCL1 signaling. J Exp Clin Cancer Res. 2023;42:129.
Google Scholar
Yang MW, Tao LY, Jiang YS, Yang JY, Huo YM, Liu DJ, et al. Perineural invasion reprograms the immune microenvironment through cholinergic signaling in pancreatic ductal adenocarcinoma. Cancer Res. 2020;80:1991–2003.
Google Scholar
Pan J, Zhang L, Wang X, Li L, Yang C, Wang Z, 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;42:255.
Google Scholar
Pan C, Wu J, Zheng S, Sun H, Fang Y, Huang Z, et al. Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β2 -AR/MACC1 axis. Cancer Commun. 2021;41:1049–70.
Google Scholar
Zhang X, Zhang Y, He Z, Yin K, Li B, Zhang L, et al. Chronic stress promotes gastric cancer progression and metastasis: an essential role for ADRB2. Cell Death Dis. 2019;10:788.
Google Scholar
Tan KW, Chong SZ, Wong FH, Evrard M, Tan SM, Keeble J, et al. Neutrophils contribute to inflammatory lymphangiogenesis by increasing VEGF-A bioavailability and secreting VEGF-D. Blood. 2013;122:3666–77.
Google Scholar
Zhang Q, Liu S, Wang H, Xiao K, Lu J, Chen S, et al. ETV4 mediated tumor-associated neutrophil infiltration facilitates lymphangiogenesis and lymphatic metastasis of bladder cancer. Adv Sci. 2023;10:e2205613.
Google Scholar
Yu J, Fu Y, Gao J, Zhang Q, Zhang N, Zhang Z, et al. Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury. Redox Biol. 2024;74:103231.
Google Scholar
Xu ZP, Song Y, Yang K, Zhou W, Hou LN, Zhu L, et al. M3 mAChR-mediated IL-8 expression through PKC/NF-κB signaling pathways. Inflamm Res. 2014;63:463–73.
Google Scholar
Chen H, Guo G, Yang G. CD300ld: a new target for tumor immunotherapy and new hope for cancer patients. Sci Bull. 2024;69:2653–5.
Google Scholar
Zhang LZ, He X, Zhu HD. Targeting CD300ld to normalize the tumor microenvironment: an emerging insight in cancer immunotherapy. MedComm. 2024;5:e607.
Google Scholar
Bresnick AR, Weber DJ, Zimmer DB. S100 proteins in cancer. Nat Rev Cancer. 2015;15:96–109.
Google Scholar
Shi G, Cao Y, Xu J, Chen B, Zhang X, Zhu Y, et al. Inhibition of S100A8/A9 ameliorates neuroinflammation by blocking NET formation following traumatic brain injury. Redox Biol. 2025;81:103532.
Google Scholar
Zhang Y, Zhang W, Ma M, Zhang X, Li C, Deng T, et al. Corydalis yanhusuo extract and its pharmacological substances alleviate food allergy by inhibiting mast cells activation via PLC/PKC/STAT3 pathway. J Ethnopharmacol. 2025;337:118809.
Google Scholar
Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, et al. Nerve growth factor promotes gastric tumorigenesis through aberrant cholinergic signaling. Cancer Cell. 2017;31:21–34.
Zhi X, Wu F, Qian J, Ochiai Y, Lian G, Malagola E, et al. Nociceptive neurons promote gastric tumour progression via a CGRP-RAMP1 axis. Nature. 2025;640:802–10.
Google Scholar
Ma L, Lei L, Eng SR, Turner E, Parada LF. Brn3a regulation of TrkA/NGF receptor expression in developing sensory neurons. Development. 2003;130:3525–34.
Google Scholar
Lee S, Hwang C, Marini S, Tower RJ, Qin Q, Negri S, et al. NGF-TrkA signaling dictates neural ingrowth and aberrant osteochondral differentiation after soft tissue trauma. Nat Commun. 2021;12:4939.
Google Scholar
Berthoud HR, Neuhuber WL. Functional and chemical anatomy of the afferent vagal system. Auton Neurosci. 2000;85:1–17.
Google Scholar
Zhan X, Wu R, Kong XH, You Y, He K, Sun XY, et al. Elevated neutrophil extracellular traps by HBV-mediated S100A9-TLR4/RAGE-ROS cascade facilitate the growth and metastasis of hepatocellular carcinoma. Cancer Commun. 2023;43:225–45.
Google Scholar
Chen X, Cheng G, Zhu L, Liu T, Yang X, Liu R, et al. Alarmin S100A8 imparts chemoresistance of esophageal cancer by reprogramming cancer-associated fibroblasts. Cell Rep Med. 2024;5:101576.
Google Scholar
Chen Y, Yang X, Kinoshita R, Tomonobu N, Pan B, Wu F, et al. S100A8/A9-MCAM signaling promotes gastric cancer cell progression via ERK-c-Jun activation. In Vitro Cell Dev Biol Anim. 2025;61:1082–96.
Wang L, Chang EW, Wong SC, Ong SM, Chong DQ, Ling KL. Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol. 2013;190:794–804.
Google Scholar

