التفاصيل البيبلوغرافية
| العنوان: |
Deciphering glioma intrinsic transcriptional subtypes identifies tumor evolution associates with changes in immune-microenvironment |
| المؤلفون: |
Wang, Q H, Hu, B L, Hu, X, Squatrito, M, Scarpace, Lisa, de Carvalho, Ana C, Lyu, S, Li, P P, Li, Y, Barthel, F P, Cho, HJ, Lin, Y H, Satani, N, Martinez-Ledesma, E, Zheng, S Y, Chang, E, Olar, A, Lan, Z D, Finocchiaro, G, Phillips, J J, Berger, M S, Gabrusiewicz, K, Wang, G C, Eskilsson, E, Hu, J, Mikkelsen, Tom, Depinho, R, Muller, F, Heimberger, A, Sullman, E, Nam, D H, Verhaak, R |
| المصدر: |
Neurosurgery Meeting Abstracts |
| بيانات النشر: |
Henry Ford Health Scholarly Commons |
| سنة النشر: |
2017 |
| المجموعة: |
Henry Ford Health System Scholarly Commons |
| الوصف: |
Glioblastoma expression subtypes have been previously been associated with genomic abnormalities, treatment response, and differences in tumor microenvironment. We leveraged IDH wild-type glioblastomas, derivative neurospheres, and single cell gene expression profiles to define three tumor-intrinsic transcriptional subtypes designated as proneural, mesenchymal, and classical, a revision of the previously reported TCGA subtypes. Transcriptomic subtype multiplicity correlated with increased intratumoral heterogeneity and the presence of tumor microenvironment. In silico cell sorting identified macrophages/microglia, CD4+ T lymphocytes, and neutrophils in the glioma microenvironment. NF1 deficiency resulted in increased tumor-associated macrophages/microglia infiltration. Comparison of matching primary and recurrent gliomas elucidated treatment-induced phenotypic tumor evolution, including expression subtype switching, in 45% of our cohort as well as associations between microenvironmental components and treatment response. Gene signature-based tumor microenvironment inference revealed a decrease in invading monocytes and a subtype-dependent increase in macrophages/microglia cells upon disease recurrence. Hypermutation at diagnosis or at recurrence was associated with CD8+ T cell enrichment. Frequency of M2 macrophage detection was associated with short-term relapse after radiation therapy. Our study provides a comprehensive transcriptional and cellular landscape of IDH wild-type glioblastoma during treatment modulated tumor evolution. Characterization of the evolving glioblastoma transcriptome and tumor microenvironment aids in designing more effective immunotherapy trials. |
| نوع الوثيقة: |
text |
| اللغة: |
unknown |
| العلاقة: |
https://scholarlycommons.henryford.com/neurosurgery_mtgabstracts/47Test |
| الإتاحة: |
https://scholarlycommons.henryford.com/neurosurgery_mtgabstracts/47Test |
| رقم الانضمام: |
edsbas.56E5B9B6 |
| قاعدة البيانات: |
BASE |
