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; David M. Ashley

doi:10.1038/s41467-020-20469-6

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. LippSmita K. Nair, Mustafa Khasraw, Katherine B. Peters, Dina Randazzo, John H. Sampson, Roger E. McLendon, Darell D. Bigner, David M. Ashley

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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.

Original language	English (US)
Article number	352
Journal	Nature communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20469-6
State	Published - Dec 1 2021
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Gromeier, M., Brown, M. C., Zhang, G., Lin, X., Chen, Y., Wei, Z., Beaubier, N., Yan, H., He, Y., Desjardins, A., Herndon, J. E., Varn, F. S., Verhaak, R. G., Zhao, J., Bolognesi, D. P., Friedman, A. H., Friedman, H. S., McSherry, F., Muscat, A. M., ... Ashley, D. M. (2021). Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy. Nature communications, 12(1), Article 352. https://doi.org/10.1038/s41467-020-20469-6

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title = "Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy",

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 na{\"i}ve 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.",

author = "Matthias Gromeier and Brown, {Michael C.} and Gao Zhang and Xiang Lin and Yeqing Chen and Zhi Wei and Nike Beaubier and Hai Yan and Yiping He and Annick Desjardins and Herndon, {James E.} and Varn, {Frederick S.} and Verhaak, {Roel G.} and Junfei Zhao and Bolognesi, {Dani P.} and Friedman, {Allan H.} and Friedman, {Henry S.} and Frances McSherry and Muscat, {Andrea M.} and Lipp, {Eric S.} and Nair, {Smita K.} and Mustafa Khasraw and Peters, {Katherine B.} and Dina Randazzo and Sampson, {John H.} and McLendon, {Roger E.} and Bigner, {Darell D.} and Ashley, {David M.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41467-020-20469-6",

language = "English (US)",

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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 2021, 'Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy', Nature communications, vol. 12, no. 1, 352. https://doi.org/10.1038/s41467-020-20469-6

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AU - Gromeier, Matthias

AU - Brown, Michael C.

AU - Zhang, Gao

AU - Lin, Xiang

AU - Chen, Yeqing

AU - Wei, Zhi

AU - Beaubier, Nike

AU - Yan, Hai

AU - He, Yiping

AU - Desjardins, Annick

AU - Herndon, James E.

AU - Varn, Frederick S.

AU - Verhaak, Roel G.

AU - Zhao, Junfei

AU - Bolognesi, Dani P.

AU - Friedman, Allan H.

AU - Friedman, Henry S.

AU - McSherry, Frances

AU - Muscat, Andrea M.

AU - Lipp, Eric S.

AU - Nair, Smita K.

AU - Khasraw, Mustafa

AU - Peters, Katherine B.

AU - Randazzo, Dina

AU - Sampson, John H.

AU - McLendon, Roger E.

AU - Bigner, Darell D.

AU - Ashley, David M.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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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JO - Nature communications

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

Abstract

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