The current status and future of PD-L1 in liver cancer

Front Immunol. 2023 Dec 12:14:1323581. doi: 10.3389/fimmu.2023.1323581. eCollection 2023.

Abstract

The application of immunotherapy in tumor, especially immune checkpoint inhibitors (ICIs), has played an important role in the treatment of advanced unresectable liver cancer. However, the efficacy of ICIs varies greatly among different patients, which has aroused people's attention to the regulatory mechanism of programmed death ligand-1 (PD-L1) in the immune escape of liver cancer. PD-L1 is regulated by multiple levels and signaling pathways in hepatocellular carcinoma (HCC), including gene variation, epigenetic inheritance, transcriptional regulation, post-transcriptional regulation, and post-translational modification. More studies have also found that the high expression of PD-L1 may be the main factor affecting the immunotherapy of liver cancer. However, what is the difference of PD-L1 expressed by different types of cells in the microenvironment of HCC, and which type of cells expressed PD-L1 determines the effect of tumor immunotherapy remains unclear. Therefore, clarifying the regulatory mechanism of PD-L1 in liver cancer can provide more basis for liver cancer immunotherapy and combined immune treatment strategy. In addition to its well-known role in immune regulation, PD-L1 also plays a role in regulating cancer cell proliferation and promoting drug resistance of tumor cells, which will be reviewed in this paper. In addition, we also summarized the natural products and drugs that regulated the expression of PD-L1 in HCC.

Keywords: HCC; PD-L1; cancer; hepatocellular carcinoma; liver cancer.

Publication types

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

MeSH terms

  • B7-H1 Antigen / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / therapy
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / therapy
  • Tumor Microenvironment

Substances

  • B7-H1 Antigen

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The present study was financially supported by the Science and Technology Program of Hebei (223777156D); National Natural Science Foundation of China (81973840 and 81273748); National science and Technology major projects of the 13th Five-Year Plan (2018ZX10303502); Sichuan Provincial Administration of Traditional Chinese Medicine Major science and technology projects (2021XYCZ004).