Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy
Document Type
Article
Publication Date
12-1-2021
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.
Identifier
85099416307 (Scopus)
Publication Title
Nature Communications
External Full Text Location
https://doi.org/10.1038/s41467-020-20469-6
e-ISSN
20411723
PubMed ID
33441554
Issue
1
Volume
12
Grant
W81XWH-16-1-0354
Fund Ref
National Institutes of Health
Recommended Citation
Gromeier, Matthias; Brown, Michael C.; Zhang, Gao; Lin, Xiang; Chen, Yeqing; Wei, Zhi; Beaubier, Nike; Yan, Hai; He, Yiping; Desjardins, Annick; Herndon, James E.; Varn, Frederick S.; Verhaak, Roel G.; Zhao, Junfei; Bolognesi, Dani P.; Friedman, Allan H.; Friedman, Henry S.; and McSherry, Frances, "Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy" (2021). Faculty Publications. 3653.
https://digitalcommons.njit.edu/fac_pubs/3653
