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GeoMx Digital Spatial Profiling of 80 proteins and 1,833 messenger RNA targets in the polyp stroma and the whole transcriptome (18,815 messenger RNA targets) in polyp epithelia was undertaken on sinonasal biopsies collected from 20 individuals with eosinophilic CRSwNP before and after 16 and 24 wk of mepolizumab treatment. Anti-IL5 therapy in patients with eosinophilic CRSwNP had significant tissue biological impact. Treatment-related changes in polyp stroma proteins associated with checkpoint inhibition (PD-1), neutrophil degranulation (CD6b, CD44, STING1), and the innate immune system (CD14, CD68, STING, CD163) were identified in a protein interaction network. Transcriptionally, there were significant reductions in gene sets associated with the reactome terms \u201cinnate and adaptive immune system,\u201d \u201cneutrophil degranulation,\u201d and \u201cTGF\u03b2 receptor signaling in epithelial-to-mesenchymal transition within polyp stroma,\u201d as well as \u201cenhancing antioxidant pathways.\u201d In polyp epithelia, increases in gene sets associated with the reactome terms \u201ccilium assembly\u201d and \u201ckeratinization\u201d and a reduction in the regulation of KIT signaling were observed. Spatial profiling demonstrates that the effects of anti-IL5 treatment within nasal polyp tissue extend beyond simple eosinophil reduction to regulation of innate and adaptive immune cells and in improving epithelial barrier biology. The clinical relevance of changes to improved barrier function may relate to quality-of-life metrics observed previously with anti-IL5 treatment.<\/jats:p>","DOI":"10.1093\/jleuko\/qiaf128","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T06:16:34Z","timestamp":1757398594000},"source":"Crossref","is-referenced-by-count":3,"title":["Spatial profiling reveals complex cellular responses of anti-IL5 treatment with mepolizumab in eosinophilic chronic rhinosinusitis with nasal polyposis"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5482-4182","authenticated-orcid":false,"given":"Nicholas P","family":"West","sequence":"first","affiliation":[{"name":"School of Pharmacy and Medical Science and Central Facility for Genomics, Griffith University , Gold Coast Campus, Parklands Drive, QLD 4215 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M","family":"Williams","sequence":"additional","affiliation":[{"name":"QFAB Bioinformatics, Services Road, The University of Queensland , St Lucia, Brisbane, QLD 4067 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Sinclair","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science and Central Facility for Genomics, Griffith University , Gold Coast Campus, Parklands Drive, QLD 4215 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Howarth","sequence":"additional","affiliation":[{"name":"Global Medical, Specialty Care , GSK, 980 Great West Road, Brentford, London WC1A 1DG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter K","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Medicine and Dentistry, Gold Coast Campus, Griffith University , Parklands Drive, QLD 4215 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Alvarado","sequence":"additional","affiliation":[{"name":"Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, University of New South Wales , Darlinghurst, Sydney, NSW 2011 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Earls","sequence":"additional","affiliation":[{"name":"Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, University of New South Wales , Darlinghurst, Sydney, NSW 2011 ,","place":["Australia"]},{"name":"Department of Anatomical Pathology, St Vincent's Hospital , 390 Victoria Street, Sydney, Darlinghurst, NSW 2010 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J","family":"Harvey","sequence":"additional","affiliation":[{"name":"Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, 405 Liverpool Street, University of New South Wales , Darlinghurst, Sydney, NSW 2011 ,","place":["Australia"]},{"name":"Faculty of Medicine and Health Sciences, Macquarie University , Balaclava Road, Sydney, NSW 2109 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J","family":"Cox","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Science and Central Facility for Genomics, Griffith University , Gold Coast Campus, Parklands Drive, QLD 4215 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"2026040207424920600_qiaf128-B1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4168\/aair.2021.13.1.8","article-title":"Biology and function of eosinophils in chronic rhinosinusitis with or without nasal 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