Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.
Biomarkers, Tumor
/ genetics
Brain Neoplasms
/ genetics
Cohort Studies
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Genomics
/ methods
Glioblastoma
/ genetics
Humans
Immunotherapy
/ methods
Inflammation
/ genetics
Mutation
Neoplasm Recurrence, Local
Oncolytic Virotherapy
/ methods
Outcome Assessment, Health Care
/ methods
Proportional Hazards Models
Survival Analysis
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
13 01 2021
13 01 2021
Historique:
received:
21
08
2020
accepted:
30
11
2020
entrez:
14
1
2021
pubmed:
15
1
2021
medline:
2
2
2021
Statut:
epublish
Résumé
Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.
Identifiants
pubmed: 33441554
doi: 10.1038/s41467-020-20469-6
pii: 10.1038/s41467-020-20469-6
pmc: PMC7806846
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
352Subventions
Organisme : NCI NIH HHS
ID : P50 CA190991
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA197264
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA154291
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS099463
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS112899
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS108773
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA225622
Pays : United States
Organisme : NCI NIH HHS
ID : F32 CA224593
Pays : United States
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