Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gromeier, M; Brown, MC; Zhang, G; Lin, X; Chen, Y; Wei, Z; Beaubier, N; Yan, H; He, Y; Desjardins, A; Herndon, JE; Varn, FS; Verhaak, RG; Zhao, J; Bolognesi, DP; Friedman, AH; Friedman, HS; McSherry, F; Muscat, AM; Lipp, ES; Nair, SK; Khasraw, M; Peters, KB; Randazzo, D; Sampson, JH; McLendon, RE; Bigner, DD; Ashley, DM

Published Date

  • January 13, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 352 -

PubMed ID

  • 33441554

Pubmed Central ID

  • PMC7806846

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-20469-6


  • eng

Conference Location

  • England