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

Matthias Gromeier, Michael C. Brown, Gao Zhang, Xiang Lin, Yeqing Chen, Zhi Wei, Nike Beaubier, Hai Yan, Yiping He, Annick Desjardins, James E. Herndon, Frederick S. Varn, Roel G. Verhaak, Junfei Zhao, Dani P. Bolognesi, Allan H. Friedman, Henry S. Friedman, Frances McSherry, Andrea M. Muscat, Eric S. Lipp, Smita K. Nair, Mustafa Khasraw, Katherine B. Peters, Dina Randazzo, John H. Sampson, Roger E. McLendon, Darell D. Bigner and David M. Ashley ()
Additional contact information
Matthias Gromeier: Duke University Medical Center
Michael C. Brown: Duke University Medical Center
Gao Zhang: Duke University Medical Center
Xiang Lin: Department of Computer Science at the New Jersey Institute of Technology
Yeqing Chen: Department of Computer Science at the New Jersey Institute of Technology
Zhi Wei: Department of Computer Science at the New Jersey Institute of Technology
Nike Beaubier: Tempus Labs, Inc.
Hai Yan: The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Yiping He: The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Annick Desjardins: Duke University Medical Center
James E. Herndon: The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Frederick S. Varn: The Jackson Laboratory for Genomic Medicine
Roel G. Verhaak: The Jackson Laboratory for Genomic Medicine
Junfei Zhao: Department of Systems Biology at Columbia University
Dani P. Bolognesi: Duke University Medical Center
Allan H. Friedman: Duke University Medical Center
Henry S. Friedman: Duke University Medical Center
Frances McSherry: Duke University Medical Center
Andrea M. Muscat: Deakin University
Eric S. Lipp: Duke University Medical Center
Smita K. Nair: Duke University Medical Center
Mustafa Khasraw: Duke University Medical Center
Katherine B. Peters: Duke University Medical Center
Dina Randazzo: Duke University Medical Center
John H. Sampson: Duke University Medical Center
Roger E. McLendon: The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
Darell D. Bigner: Duke University Medical Center
David M. Ashley: Duke University Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-7

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-020-20469-6

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