{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T05:11:52Z","timestamp":1780377112390,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371169"],"award-info":[{"award-number":["82371169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Glia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vestibular schwannoma (VS) is a benign tumor originating from the vestibular nerve, and its complex tumor microenvironment presents significant challenges for research. This study employs single\u2010cell transcriptome sequencing to comprehensively investigate the molecular characteristics of Schwann cells within VS and their potential immunoregulatory roles in the tumor microenvironment. We identified a novel subpopulation of Schwann cells, termed Schwann 4, which shows significantly expressed MHC class II molecules and co\u2010enrichment of PI3K signaling, focal adhesion, and cell adhesion\u2010related pathways, suggesting its potential involvement in tumor\u2010immune modulation. Utilizing machine learning models, we pinpointed 179 genes significantly expressed in Schwann 4, with CTSZ emerging as a candidate gene. CTSZ expression is elevated in VS and is significantly correlated with the PI3K pathway. Comparative analysis revealed that CTSZ promotes proliferation in malignant CNS tumors, whereas its role in benign VS appears distinct. Experimental analysis revealed that CTSZ is correlated with regulatory T cells (Tregs) functionality markers via the PVR\u2010TIGIT pathway, suggesting a potential mechanism for Schwann cell\u2010mediated immune modulation. Functional assays further demonstrated that CTSZ knockdown impairs cell migration and focal adhesion kinase activity. Drug sensitivity analyses identified candidate agents such as YM201636 and AT7867, though their applicability to VS requires dedicated validation. This study contributes to understanding the molecular mechanisms of Schwann cells in benign nerve sheath tumors while providing preliminary evidence for future therapeutic investigation.<\/jats:p>","DOI":"10.1002\/glia.70179","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:46:16Z","timestamp":1780375576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Characterization and Immune Modulation of Schwann Cells in Vestibular Schwannoma"],"prefix":"10.1002","volume":"74","author":[{"given":"Lu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Integrated Traditional Chinese and Western Medicine Second Hospital Affiliated With Hunan University of Chinese Medicine  Liuyang Hunan China"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province  Changsha Hunan China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijiang","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province  Changsha Hunan China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6409-9089","authenticated-orcid":false,"given":"Guowei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province  Changsha Hunan China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"He","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province  Changsha Hunan China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Xiangya Hospital Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuewen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery, Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Otolaryngology Major Disease Research Key Laboratory of Hunan Province  Changsha Hunan China"},{"name":"Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province  Changsha Hunan China"},{"name":"National Clinical Research Center for Geriatric Disorders (Xiangya Hospital)  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"issue":"3","key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.immuni.2022.02.005","article-title":"Mechanistic Convergence of the TIGIT and PD\u20101 Inhibitory Pathways Necessitates Co\u2010Blockade to Optimize Anti\u2010Tumor CD8(+) T Cell Responses","volume":"55","author":"Banta K. L.","year":"2022","journal-title":"Immunity"},{"issue":"1","key":"e_1_2_13_3_1","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1038\/s41467-023-42762-w","article-title":"Single\u2010Cell Multi\u2010Omic Analysis of the Vestibular Schwannoma Ecosystem Uncovers a Nerve Injury\u2010Like State","volume":"15","author":"Barrett T. F.","year":"2024","journal-title":"Nature Communications"},{"issue":"10","key":"e_1_2_13_4_1","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1038\/s41416-024-02646-2","article-title":"Single\u2010Cell RNA Sequencing Analysis of Vestibular Schwannoma Reveals Functionally Distinct Macrophage Subsets","volume":"130","author":"Baruah P.","year":"2024","journal-title":"British Journal of Cancer"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.nbd.2022.105952","article-title":"Schwann Cell Functions in Peripheral Nerve Development and Repair","volume":"176","author":"Bosch\u2010Queralt M.","year":"2023","journal-title":"Neurobiology of Disease"},{"issue":"14","key":"e_1_2_13_6_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1056\/NEJMra2020394","article-title":"Vestibular Schwannomas","volume":"384","author":"Carlson M. L.","year":"2021","journal-title":"New England Journal of Medicine"},{"issue":"2","key":"e_1_2_13_7_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1053\/j.gastro.2020.03.074","article-title":"Hepatocellular Carcinoma Cells Up\u2010Regulate PVRL1, Stabilizing PVR and Inhibiting the Cytotoxic T\u2010Cell Response via TIGIT to Mediate Tumor Resistance to PD1 Inhibitors in Mice","volume":"159","author":"Chiu D. K.","year":"2020","journal-title":"Gastroenterology"},{"issue":"4","key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1007\/s12105-020-01155-x","article-title":"Vestibular Schwannoma: What we Know and Where we Are Heading","volume":"14","author":"Gupta V. 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