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

Author

Listed:
  • Matthias Gromeier

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Michael C. Brown

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Gao Zhang

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at 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
    Duke University Medical Center)

  • Yiping He

    (The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
    Duke University Medical Center)

  • Annick Desjardins

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • James E. Herndon

    (The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
    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
    Istari Oncology Inc.)

  • Allan H. Friedman

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Henry S. Friedman

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Frances McSherry

    (Duke University Medical Center)

  • Andrea M. Muscat

    (Deakin University)

  • Eric S. Lipp

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Smita K. Nair

    (Duke University Medical Center)

  • Mustafa Khasraw

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Katherine B. Peters

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Dina Randazzo

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • John H. Sampson

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • Roger E. McLendon

    (The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center
    Duke University Medical Center)

  • Darell D. Bigner

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

  • David M. Ashley

    (Duke University Medical Center
    The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center)

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.

Suggested Citation

  • 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 , 2021. "Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy," Nature Communications, Nature, vol. 12(1), pages 1-7, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20469-6
    DOI: 10.1038/s41467-020-20469-6
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    Cited by:

    1. Shannon Coy & Shu Wang & Sylwia A. Stopka & Jia-Ren Lin & Clarence Yapp & Cecily C. Ritch & Lisa Salhi & Gregory J. Baker & Rumana Rashid & Gerard Baquer & Michael Regan & Prasidda Khadka & Kristina A, 2022. "Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma," Nature Communications, Nature, vol. 13(1), pages 1-24, December.

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