Harnessing radiation biology to augment immunotherapy for glioblastoma

Karishma R. Rajani, Lucas P. Carlstrom, Ian F Parney, Aaron J. Johnson, Arthur E. Warrington, Terence Burns

Research output: Contribution to journalArticle

Abstract

Glioblastoma is the most common adult primary brain tumor and carries a dismal prognosis. Radiation is a standard first-line therapy, typically deployed following maximal safe surgical debulking, when possible, in combination with cytotoxic chemotherapy. For other systemic cancers, standard of care is being transformed by immunotherapies, including checkpoint-blocking antibodies targeting CTLA-4 and PD-1/PD-L1, with potential for long-term remission. Ongoing studies are evaluating the role of immunotherapies for GBM. Despite dramatic responses in some cases, randomized trials to date have not met primary outcomes. Challenges have been attributed in part to the immunologically "cold" nature of glioblastoma relative to other malignancies successfully treated with immunotherapy. Radiation may serve as a mechanism to improve tumor immunogenicity. In this review, we critically evaluate current evidence regarding radiation as a synergistic facilitator of immunotherapies through modulation of both the innate and adaptive immune milieu. Although current preclinical data encourage efforts to harness synergistic biology between radiation and immunotherapy, several practical and scientific challenges remain. Moreover, insights from radiation biology may unveil additional novel opportunities to help mobilize immunity against GBM.

Original languageEnglish (US)
Article number656
JournalFrontiers in Oncology
Volume9
Issue numberFEB
DOIs
StatePublished - Jan 1 2019

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Radiobiology
Glioblastoma
Immunotherapy
Radiation
Neoplasms
Blocking Antibodies
Standard of Care
Brain Neoplasms
Immunity
Drug Therapy

Keywords

  • CTLA-4
  • GBM
  • Glioblastoma
  • Immunotherapies
  • Innate and adaptive immune responses
  • PD-1/PD-L1
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Harnessing radiation biology to augment immunotherapy for glioblastoma. / Rajani, Karishma R.; Carlstrom, Lucas P.; Parney, Ian F; Johnson, Aaron J.; Warrington, Arthur E.; Burns, Terence.

In: Frontiers in Oncology, Vol. 9, No. FEB, 656, 01.01.2019.

Research output: Contribution to journalArticle

Rajani, Karishma R. ; Carlstrom, Lucas P. ; Parney, Ian F ; Johnson, Aaron J. ; Warrington, Arthur E. ; Burns, Terence. / Harnessing radiation biology to augment immunotherapy for glioblastoma. In: Frontiers in Oncology. 2019 ; Vol. 9, No. FEB.
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