Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.
Document Type
Article
Publication Date
1-13-2021
Keywords
JGM
JAX Source
Nat Commun 2021 Jan 13; 12(1):352
Volume
12
Issue
1
First Page
352
Last Page
352
ISSN
2041-1723
PMID
33441554
DOI
https://doi.org/10.1038/s41467-020-20469-6
Abstract
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.
Recommended Citation
Gromeier M,
Brown M,
Zhang G,
Lin X,
Chen Y,
Wei Z,
Beaubier N,
Yan H,
He Y,
Desjardins A,
Herndon J,
Varn F,
Verhaak R,
Zhao J,
Bolognesi D,
Friedman A,
Friedman H,
McSherry F,
Muscat A,
Lipp E,
Nair S,
Khasraw M,
Peters K,
Randazzo D,
Sampson J,
McLendon R,
Bigner D,
Ashley D.
Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy. Nat Commun 2021 Jan 13; 12(1):352
Comments
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