A novel in situ multiplex immunofluorescence panel for the assessment of tumor immunopathology and response to virotherapy in pediatric glioblastoma reveals a role for checkpoint protein inhibition

Joshua D. Bernstock, Nunzio Vicario, Li Rong, Pablo A. Valdes, Bryan D. Choi, Jason A. Chen, Daniel DiToro, Diana S. Osorio, Kara Kachurak, Florian Gessler, James M. Johnston, T. Prescott Atkinson, Richard J. Whitley, Asim K. Bag, G. Yancey Gillespie, James M. Markert, Dragan Maric, Gregory K. Friedman

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Immunotherapy with oncolytic herpes simplex virus-1 therapy offers an innovative, targeted, less-toxic approach for treating brain tumors. However, a major obstacle in maximizing oncolytic virotherapy is a lack of comprehensive understanding of the underlying mechanisms that unfold in CNS tumors/associated microenvironments after infusion of virus. We demonstrate that our multiplex biomarker screening platform comprehensively informs changes in both topographical location and functional states of resident/infiltrating immune cells that play a role in neuropathology after treatment with HSV G207 in a pediatric Phase 1 patient. Using this approach, we identified robust infiltration of CD8+ T cells suggesting activation of the immune response following virotherapy; however there was a corresponding upregulation of checkpoint proteins PD-1, PD-L1, CTLA-4, and IDO revealing a potential role for checkpoint inhibitors. Such work may ultimately lead to an understanding of the governing pathobiology of tumors, thereby fostering development of novel therapeutics tailored to produce optimal responses.

Original languageEnglish (US)
Article numbere1678921
JournalOncoImmunology
Volume8
Issue number12
DOIs
StatePublished - Dec 2 2019
Externally publishedYes

Keywords

  • checkpoint proteins
  • glioma
  • HSV
  • multiplex immunofluorescence
  • oncolytic virotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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