{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T18:02:04Z","timestamp":1781028124288,"version":"3.54.1"},"reference-count":197,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":148,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NF2 BioSolutions"},{"DOI":"10.13039\/501100022431","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/T016515\/1"],"award-info":[{"award-number":["MR\/T016515\/1"]}],"id":[{"id":"10.13039\/501100022431","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022431","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W028867\/1"],"award-info":[{"award-number":["MR\/W028867\/1"]}],"id":[{"id":"10.13039\/501100022431","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Neurofibromatosis type 2-related schwannomatosis is a rare tumour predisposition syndrome caused by loss-of-function pathogenic variants within the NF2 gene, which encodes the tumour suppressor protein merlin. This leads to development of benign tumours within the nervous system, most notably vestibular schwannomas that form on the vestibulocochlear (eighth cranial) nerve. Whilst the merlin-regulated molecular mechanisms in neoplastic Schwann cells that underlie vestibular schwannoma formation and growth are increasingly understood, the role of the tumour-immune microenvironment\u2014particularly T-cells\u2014in influencing vestibular schwannoma pathology and the clinical trajectory of disease remain understudied. In this review, we outline fundamental principles of T-cell immunobiology and anti-tumour immunity and examine their relevance to neurofibromatosis type-2-related schwannomatosis-associated vestibular schwannoma. We describe how spatial and transcriptomic profiling of tumour-infiltrating lymphocytes have revealed hallmarks of T-cell exhaustion and immunoevasion within vestibular schwannoma tumours and the existence of myriad immunosuppressive mechanisms within the vestibular schwannoma microenvironment\u2014including immune checkpoint ligand expression, immunosuppressive cytokines, regulatory immune subsets and metabolic constraints. We also review the key remaining biological prerequisites, such as T-cell dynamics, T-cell functional state and T-cell spatial context within the tumour microenvironment, that must be addressed before advanced T-cell-based strategies can be rationally developed for vestibular schwannoma.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag192","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:46:03Z","timestamp":1779882363000},"source":"Crossref","is-referenced-by-count":0,"title":["T-cell-targeted immunotherapy in neurofibromatosis type 2-related vestibular schwannoma: current evidence and future direction"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7811-8313","authenticated-orcid":false,"given":"Reygn J","family":"Done","sequence":"first","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Division of Immunology, Immunity and Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Ahmid","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Division of Neuroscience, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3184-0817","authenticated-orcid":false,"given":"Miriam J","family":"Smith","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Manchester Centre for Genomic Medicine, St Mary\u2019s Hospital, Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D Gareth","family":"Evans","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Manchester Centre for Genomic Medicine, St Mary\u2019s Hospital, Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar N","family":"Pathmanaban","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Division of Neuroscience, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust , Salford M6 8HD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brough","sequence":"additional","affiliation":[{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Division of Neuroscience, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin N","family":"Couper","sequence":"additional","affiliation":[{"name":"Lydia Becker Institute of Immunology and Inflammation, Division of Immunology, Immunity and Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester , Manchester M13 9PT ,","place":["UK"]},{"name":"Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester , Manchester M13 9PT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"issue":"11","key":"2026060913341133100_fcag192-B1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22115850","article-title":"Current understanding of neurofibromatosis type 1, 2, and schwannomatosis","volume":"22","author":"Tamura","year":"2021","journal-title":"Int J Mol Sci"},{"issue":"9","key":"2026060913341133100_fcag192-B2","doi-asserted-by":"crossref","first-page":"1967","DOI":"10.1016\/j.gim.2022.05.007","article-title":"Updated diagnostic criteria and nomenclature for neurofibromatosis type 2 and schwannomatosis: An international consensus recommendation","volume":"24","author":"Plotkin","year":"2022","journal-title":"Genet Med"},{"issue":"6136","key":"2026060913341133100_fcag192-B3","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/329246a0","article-title":"Genetic linkage of bilateral acoustic neurofibromatosis 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