HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

Chen Shen; Mei Li; Yujuan Duan; Xin Jiang; Xiaoming Hou; Fulai Xue; Yinan Zhang; Yao Luo

doi:10.3389/fimmu.2023.1170207

HDAC inhibitors enhance the anti-tumor effect of immunotherapies in hepatocellular carcinoma

Front Immunol. 2023 May 26:14:1170207. doi: 10.3389/fimmu.2023.1170207. eCollection 2023.

Authors

Chen Shen¹, Mei Li¹, Yujuan Duan^{2

3}, Xin Jiang¹, Xiaoming Hou¹, Fulai Xue¹, Yinan Zhang², Yao Luo¹

Affiliations

¹ Department of Laboratory Medicine, Medical Equipment Innovation Research Center/Medical Device Regulatory Research and Evaluation Center, West China Hospital, Sichuan University, Chengdu, China.
² School of Chemical Science and Engineering, Tongji University, Shanghai, China.
³ School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Hepatocellular carcinoma (HCC), the most common liver malignancy with a poor prognosis and increasing incidence, remains a serious health problem worldwide. Immunotherapy has been described as one of the ideal ways to treat HCC and is transforming patient management. However, the occurrence of immunotherapy resistance still prevents some patients from benefiting from current immunotherapies. Recent studies have shown that histone deacetylase inhibitors (HDACis) can enhance the efficacy of immunotherapy in a variety of tumors, including HCC. In this review, we present current knowledge and recent advances in immunotherapy-based and HDACi-based therapies for HCC. We highlight the fundamental dynamics of synergies between immunotherapies and HDACis, further detailing current efforts to translate this knowledge into clinical benefits. In addition, we explored the possibility of nano-based drug delivery system (NDDS) as a novel strategy to enhance HCC treatment.

Keywords: HDAC inhibitors; hepatocellular carcinoma; immune checkpoint inhibitors; immunotherapy; nano-based drug delivery system; tumor immune microenvironment.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Hepatocellular* / drug therapy
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Humans
Immunotherapy
Liver Neoplasms* / drug therapy
Nanoparticle Drug Delivery System

Substances

Histone Deacetylase Inhibitors
Nanoparticle Drug Delivery System

Grants and funding

This work was funded by the National Natural Science Foundation of China, No. 82003262; China Postdoctoral Science Foundation, No. 2019TQ0221 and No. 2019M663517; Post-Doctor Research Project, West China Hospital, Sichuan University, No. 2019HXBH059; Key R&D Program of Sichuan Provincial Department of Science and Technology (Major Science and Technology Project) 2022YFS0095; Sichuan University postdoctoral interdisciplinary Innovation Fund.