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Identifying the optimal choice can be difficult due to the disease\u2019s variable progression rate.<\/jats:p><jats:p>We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rapidly progressing VS was distinctly enriched in CD4<jats:sup>+<\/jats:sup>, CD8<jats:sup>+<\/jats:sup>, CD20<jats:sup>+<\/jats:sup>, and CD68<jats:sup>+<\/jats:sup>immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K\u2009\u2212\u2009Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (<jats:italic>CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3,<\/jats:italic>and<jats:italic>CXCL2-TLR6<\/jats:italic>) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13046-022-02473-4","type":"journal-article","created":{"date-parts":[[2022,10,4]],"date-time":"2022-10-04T08:03:07Z","timestamp":1664870587000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology"],"prefix":"10.1186","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-7766","authenticated-orcid":false,"given":"Moran","family":"Amit","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongxin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederico O.","family":"Gleber-Netto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam U.","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Silverman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ismail","family":"Yaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared K.","family":"Burks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory N.","family":"Fuller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W.","family":"Gidley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Elie","family":"Nader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaan M.","family":"Raza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"DeMonte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,10,4]]},"reference":[{"issue":"2","key":"2473_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11060-015-1827-9","volume":"124","author":"VR Kshettry","year":"2015","unstructured":"Kshettry VR, Hsieh JK, Ostrom QT, Kruchko C, Barnholtz-Sloan JS. 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