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- Title
Histone Deacetylase Inhibitor Panobinostat Benefits the Therapeutic Efficacy of Oncolytic Herpes Simplex Virus Combined with PD-1/PD-L1 Blocking in Glioma and Squamous Cell Carcinoma Models.
- Authors
Wu, Yinglin; Chen, Xiaoqing; Wang, Lei; Zhou, Xusha; Liu, Yonghong; Ji, Dongmei; Ren, Peigen; Zhou, Grace Guoying; Zhao, Jing
- Abstract
Background: Combination therapy has been widely explored for oncolytic virus (OV), as it can be met with tumor resistance. The HDAC inhibitor (HDACi) panobinostat is a potent pan-deacetylase inhibitor which blocks multiple cancer-related pathways and reverses epigenetic events in cancer progression. Methods: In this study, oncolytic activity in vitro and antitumor therapeutic efficacy in vivo when combined with oHSV and panobinostat were investigated. Results: (1) Treatment with panobinostat enhanced oHSV propagation and cytotoxicity in human glioma A172 and squamous cell carcinoma SCC9 cells. (2) Combined treatment with oHSV and panobinostat enhanced virus replication mediated by the transcriptional downregulation of IFN-β- and IFN-responsive antiviral genes in human glioma A172 and squamous cell carcinoma SCC9 cells. (3) Panobinostat treatment induced upregulation of PD-L1 expression in both glioma and squamous cell carcinoma cells. (4) A significantly enhanced therapeutic efficacy was shown in vivo for the murine glioma CT-2A and squamous cell carcinoma SCC7 models when treated with a combination of oHSV, including PD-1/PD-L1 blockade and HDAC inhibition. Conclusions: Consequently, these data provide some new clues for the clinical development of combination therapy with OVs, epigenetic modifiers, and checkpoint blockades for glioma and squamous cell carcinoma.
- Subjects
SQUAMOUS cell carcinoma; HERPES simplex virus; HISTONE deacetylase inhibitors; TREATMENT effectiveness; GLIOMAS; PROGRAMMED cell death 1 receptors
- Publication
Viruses (1999-4915), 2022, Vol 14, Issue 12, p2796
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v14122796