Classification of diffuse lower-grade glioma based on immunological profiling.
diffuse lower-grade glioma
immune classification
prognosis
tumor microenvironment
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
12
02
2020
revised:
10
04
2020
accepted:
05
05
2020
pubmed:
12
5
2020
medline:
7
7
2021
entrez:
12
5
2020
Statut:
ppublish
Résumé
Transcriptomic data derived from bulk sequencing have been applied to delineate the tumor microenvironment (TME) and define immune subtypes in various cancers, which may facilitate the design of immunotherapy treatment strategies. We herein gathered published gene expression data from diffuse lower-grade glioma (LGG) patients to identify immune subtypes. Based on the immune gene profiles of 402 LGG patients from The Cancer Genome Atlas, we performed consensus clustering to determine robust clusters of patients, and evaluated their reproducibility in three Chinese Glioma Genome Atlas cohorts. We further integrated immunogenomics methods to characterize the immune environment of each subtype. Our analysis identified and validated three immune subtypes-Im1, Im2, and Im3-characterized by differences in lymphocyte signatures, somatic DNA alterations, and clinical outcomes. Im1 had a higher infiltration of CD8+ T cells, Th17, and mast cells. Im2 was defined by elevated cytolytic activity, exhausted CD8+ T cells, macrophages, higher levels of aneuploidy, and tumor mutation burden, and these patients had worst outcome. Im3 displayed more prominent T helper cell and APC coinhibition signatures, with elevated pDCs and macrophages. Each subtype was associated with distinct somatic alterations. Moreover, we applied graph structure learning-based dimensionality reduction to the immune landscape and revealed significant intracluster heterogeneity with Im2 subtype. Finally, we developed and validated an immune signature with better performance of prognosis prediction. Our results demonstrated the immunological heterogeneity within diffuse LGG and provided valuable stratification for the design of future immunotherapy.
Identifiants
pubmed: 32392361
doi: 10.1002/1878-0261.12707
pmc: PMC7463381
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2081-2095Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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