Alternatively activated macrophages are associated with faster growth rate in vestibular schwannoma.

Autor:	Gregory GE; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK., Haley MJ; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.; Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK., Jones AP; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.; Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK., Hannan CJ; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Walton Centre NHS Foundation Trust, The Walton Centre, Fazakerley, Liverpool L9 7LJ, UK., Evans DG; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; Division of Evolution, Infection and Genomic Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK., King AT; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; Division of Cardiovascular Sciences, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.; Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK., Paszek P; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.; Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK.; Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-105 Warsaw, Poland., Pathmanaban ON; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.; Department of Neurosurgery, Manchester Centre for Clinical Neurosciences, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK., Couper KN; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.; Division of Immunology, Immunity to Infection and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK., Brough D; Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Foundation Trust, University of Manchester, Manchester M13 9PT, UK.; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.
Jazyk:	angličtina
Zdroj:	Brain communications [Brain Commun] 2024 Nov 12; Vol. 6 (6), pp. fcae400. Date of Electronic Publication: 2024 Nov 12 (Print Publication: 2024).
DOI:	10.1093/braincomms/fcae400
Abstrakt:	The variability in vestibular schwannoma growth rates greatly complicates clinical treatment. Management options are limited to radiological observation, surgery, radiotherapy and, in specific cases, bevacizumab therapy. As such, there is a pressing requirement for growth restricting drugs for vestibular schwannoma. This study explored potential predictors of vestibular schwannoma growth in depth, highlighting differences between static and growing vestibular schwannoma to identify potential therapeutic targets. High-dimensional imaging was used to characterize the tumour micro-environment of four static and five growing vestibular schwannoma (indicated by volumetric change < 20% or ≥ 20% per year, respectively). Single-cell spatial information and protein expression data from a panel of 35 tumour immune-targeted antibodies identified specific cell populations, their expression profiles and their spatial localization within the tumour micro-environment. Growing vestibular schwannoma contained significantly more proliferative and non-proliferative alternatively activated tumour-associated macrophages per millimetre square compared with static vestibular schwannoma. Furthermore, two additional proliferative cell types were identified in growing and static vestibular schwannoma: transitioning monocytes and programmed cell death ligand 1 (PD-L1+) Schwann cells. In agreement, growing vestibular schwannoma was characterized by a tumour micro-environment composed of immune-enriched, proliferative neighbourhoods, whereas static vestibular schwannoma were composed of tumour-enriched, non-proliferative neighbourhoods. Finally, classically activated macrophages significantly colocalized with alternatively activated macrophages in static vestibular schwannoma, but this sequestration was reduced in growing vestibular schwannoma. This study provides a novel, spatial characterization of the immune landscape in growing vestibular schwannoma, whilst highlighting the need for new therapeutic targets that modulate the tumour immune micro-environment. Competing Interests: The authors report no competing interests. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
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