دورية أكاديمية
Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes:implications for precision immunotherapy
| العنوان: | Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes:implications for precision immunotherapy |
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| المؤلفون: | White, K., Connor, K., Meylan, M., Bougoüin, A., Salvucci, M., Bielle, F., O'Farrell, A. C., Sweeney, K., Weng, L., Bergers, G., Dicker, P., Ashley, D. M., Lipp, E. S., Low, J. T., Zhao, J., Wen, P., Prins, R., Verreault, M., Idbaih, A., Biswas, A., Prehn, J. H.M., Lambrechts, D., Arijs, I., Lodi, F., Dilcan, G., Lamfers, M., Leenstra, S., Fabro, F., Ntafoulis, I., Kros, J. M., Cryan, J., Brett, F., Quissac, E., Beausang, A., MacNally, S., O'Halloran, P., Clerkin, J., Bacon, O., Kremer, A., Chi Yen, R. T., Varn, F. S., Verhaak, R. G.W., Sautès-Fridman, C., Fridman, W. H., Byrne, A. T. |
| المصدر: | White , K , Connor , K , Meylan , M , Bougoüin , A , Salvucci , M , Bielle , F , O'Farrell , A C , Sweeney , K , Weng , L , Bergers , G , Dicker , P , Ashley , D M , Lipp , E S , Low , J T , Zhao , J , Wen , P , Prins , R , Verreault , M , Idbaih , A , Biswas , A , Prehn , J H M , Lambrechts , D , Arijs , I , Lodi .... |
| سنة النشر: | 2023 |
| الوصف: | Background: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. Materials and methods: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. Results: TME High tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TME High /mesenchymal+ patients featured tertiary lymphoid structures. TME Med (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TME Low (24%) tumours were manifest as an ‘immune-desert’ group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TME High patients receiving neoadjuvant anti-PD-1 had ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://pure.eur.nl/en/publications/b94eade7-0905-4b67-aedc-c8514f107f19Test |
| DOI: | 10.1016/j.annonc.2022.11.008 |
| الإتاحة: | https://doi.org/10.1016/j.annonc.2022.11.008Test https://pure.eur.nl/en/publications/b94eade7-0905-4b67-aedc-c8514f107f19Test https://pure.eur.nl/ws/files/85458734/Identification_validation_and_biological_characterisation_of_novel_glioblastoma_tumour_microenvironment_subtypes.pdfTest http://www.scopus.com/inward/record.url?scp=85147361098&partnerID=8YFLogxKTest |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.C325B695 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.annonc.2022.11.008 |
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