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.

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.

journal_name

Oncoimmunology

journal_title

Oncoimmunology

authors

Bernstock JD,Vicario N,Rong L,Valdes PA,Choi BD,Chen JA,DiToro D,Osorio DS,Kachurak K,Gessler F,Johnston JM Jr,Atkinson TP,Whitley RJ,Bag AK,Gillespie GY,Markert JM,Maric D,Friedman GK

doi

10.1080/2162402X.2019.1678921

subject

Has Abstract

pub_date

2019-10-21 00:00:00

pages

e1678921

issue

12

eissn

2162-4011

issn

2162-402X

pii

1678921

journal_volume

8

pub_type

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