PD-L1 expression downregulation by RNF43 in gastric carcinoma enhances antitumour activity of T cells

Scand J Immunol. 2023 Jun;97(6):e13268. doi: 10.1111/sji.13268. Epub 2023 Apr 13.

Abstract

Ring finger protein 43 (RNF43), a transmembrane E3 ubiquitin ligase, has been indicated to be a potential biomarker for gastric cancer treatment, as this protein increases tumour cell apoptosis and suppresses cellular proliferation. The role of RNF43 in cellular immunotherapy remains unclear. Herein, we aimed to explore the expression level of RNF43 in gastric cancer cell lines and its role in cellular immunotherapy. The expression level of RNF43 and PD-L1 and their correlation in gastric cancer cell lines were analysed. The expression of PD-L1 was negatively correlated with that of RNF43 in gastric cancer cell lines. RNF43 interacted with PD-L1 to augment both K48- and K63-linked ubiquitination of PD-L1 in gastric cancer cell lines. In addition, RNF43 expression in gastric cancer cell lines could enhance the antitumour activity of T cells. In conclusion, this study reveals that RNF43 can inhibit PD-L1 expression to enhance the antitumour activity of cellular immunotherapy.

Keywords: PD‐L1; RNF43; cellular immunotherapy; gastric cancer; ubiquitination.

MeSH terms

  • Apoptosis
  • B7-H1 Antigen* / genetics
  • B7-H1 Antigen* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy / methods
  • Stomach Neoplasms* / immunology
  • Stomach Neoplasms* / metabolism
  • T-Lymphocytes* / immunology
  • T-Lymphocytes* / metabolism
  • Ubiquitin-Protein Ligases* / genetics
  • Ubiquitin-Protein Ligases* / metabolism
  • Ubiquitination*

Substances

  • B7-H1 Antigen
  • Ubiquitin-Protein Ligases
  • CD274 protein, human
  • RNF43 protein, human
  • DNA-Binding Proteins