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

Viruses. 2022 Dec 15;14(12):2796. doi: 10.3390/v14122796.

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.

Keywords: HDACi panobinostat; glioma; oHSV; squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-H1 Antigen / genetics
  • Carcinoma, Squamous Cell* / therapy
  • Cell Line, Tumor
  • Glioma* / metabolism
  • Glioma* / therapy
  • Histone Deacetylase Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors / therapeutic use
  • Humans
  • Mice
  • Oncolytic Virotherapy*
  • Oncolytic Viruses* / genetics
  • Panobinostat
  • Programmed Cell Death 1 Receptor
  • Simplexvirus

Substances

  • Histone Deacetylase Inhibitors
  • Panobinostat
  • Programmed Cell Death 1 Receptor
  • B7-H1 Antigen

Grants and funding

These studies were funded by grants from the China Postdoctoral Science Foundation (no. 2021M703377, Xusha Zhou), Young Scientists Fund of National Natural Science Foundation of China (no. 31900136, Yonghong Liu) to Guangzhou Medical University, and the Shenzhen Science and Innovation Commission Project Grants (no. KCXFZ202002011010232, Dongyao Ni) to the Shenzhen International Institute for Biomedical Research.