Bortezomib Treatment Sensitizes Oncolytic HSV-1-Treated Tumors to NK Cell Immunotherapy.

ABSTRACT:

Purpose

Both the proteasome inhibitor bortezomib and an oncolytic herpes simplex virus-1 (oHSV)-expressing GM-CSF are currently FDA approved. Although proteasome blockade can increase oHSV replication, immunologic consequences, and consequent immunotherapy potential are unknown. In this study, we investigated the impact of bortezomib combined with oHSV on tumor cell death and sensitivity to natural killer (NK) cell immunotherapy.

Experimental design

Western blot, flow cytometry, and caspase 3/7 activity assays were used to evaluate the induction of apoptosis/autophagy and/or necroptotic cell death. Cellular and mitochondrial reactive oxygen species (ROS) production was measured using CellROX and MitoSOX. Inhibitors/shRNA-targeting ROS, JNK and RIP1 kinase (RIPK1) were used t

SUBMITTER: Yoo JY 

PROVIDER: S-EPMC5093037 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature