Ubiquitin C-terminal hydrolase L1 promotes expression of programmed cell death-ligand 1 in non-small-cell lung cancer cells

Cancer Sci. 2020 Sep;111(9):3174-3183. doi: 10.1111/cas.14529. Epub 2020 Jul 6.

Abstract

Programmed cell death-ligand 1 (PD-L1) expressed on cancer cells can cause immune escape of non-small-cell lung cancer (NSCLC). Elucidation of the regulatory mechanisms of the PD-L1 expression is a prerequisite for establishing new tumor immunotherapy strategies. Ubiquitin C-terminal hydrolase L1 (UCHL1) is a regulator of cellular signaling transduction that is aberrantly expressed in NSCLC. However, it is not known whether UCHL1 regulates the expression of PD-L1 in NSCLC cells. In the present study, we found that UCHL1 promotes the expression of PD-L1 in NSCLC cell lines. In addition, UCHL1 expressed in NSCLC cells inhibited activation of Jurkat cells through upregulation of PD-L1 expression in in vitro experiments. Moreover, UCHL1 upregulates PD-L1 expression through facilitating activation of the AKT-P65 signaling pathway. In conclusion, these results indicated that UCHL1 promoted PD-L1 expression in NSCLC cells. This finding implied that inhibition of UCHL1 might suppress immune escape of NSCLC through downregulation of PD-L1 expression in NSCLC cells.

Keywords: AKT; NSCLC; P65; PD-L1; UCHL1.

MeSH terms

  • B7-H1 Antigen / genetics*
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunomodulation
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription Factor RelA / metabolism
  • Ubiquitin Thiolesterase / metabolism*

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Transcription Factor RelA
  • UCHL1 protein, human
  • Proto-Oncogene Proteins c-akt
  • Ubiquitin Thiolesterase