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.

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