TY  - JOUR
A1  - Bernstock, Joshua D.
A1  - Vicario, Nunzio
A1  - Rong, Li
A1  - Valdes, Pablo A.
A1  - Choi, Bryan D.
A1  - Chen, Jason A.
A1  - DiToro, Daniel
A1  - Osorio, Diana S.
A1  - Kachurak, Kara
A1  - Geßler, Florian
A1  - Johnston, James M.
A1  - Atkinson, T. Prescott
A1  - Whitley, Richard J.
A1  - Bag, Asim K.
A1  - Gillespie, G. Yancey
A1  - Markert, James M.
A1  - Maric, Dragan
A1  - Friedman, Gregory K.
T1  - 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
T2  - OncoImmunology
N2  - 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.
KW  - HSV
KW  - oncolytic virotherapy
KW  - glioma
KW  - multiplex immunofluorescence
KW  - checkpoint proteins
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53421
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-534210
SN  - 2162-402X
SN  - 2162-4011
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
VL  - 8
IS  - 12, e1678921
SP  - 1
EP  - 14
PB  - Taylor & Franics
CY  - Abingdon
ER  -