The mechanism underlying arsenic-induced PD-L1 upregulation in transformed BEAS-2B cells

Toxicol Appl Pharmacol. 2022 Jan 15:435:115845. doi: 10.1016/j.taap.2021.115845. Epub 2021 Dec 22.

Abstract

Chronic exposure to arsenic promotes lung cancer. Human studies have identified immunosuppression as a risk factor for cancer development. The immune checkpoint pathway of Programmed cell death 1 ligand (PD-L1) and its receptor (programmed cell death receptor 1, PD-1) is the most studied mechanism of immunosuppression. We have previously shown that prolonged arsenic exposure induced cell transformation of BEAS-2B cells, a human lung epithelial cell line. More recently our study further showed that arsenic induced PD-L1 up-regulation, inhibited T cell effector function, and enhanced lung tumor formation in the mice. In the current study, using arsenic-induced BEAS-2B transformation as a model system we investigated the mechanism underlying PD-L1 up-regulation by arsenic. Our data suggests that Lnc-DC, a long non-coding RNA, and signal transducer and activator of transcription 3 (STAT3) mediates PD-L1 up-regulation by arsenic.

Keywords: Arsenic; Lnc-DC; Lung; PD-L1; STAT3; Tumorigenesis; lnRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenic / toxicity*
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / genetics*
  • Cell Line
  • Female
  • Humans
  • Lung Neoplasms / chemically induced
  • Lung Neoplasms / pathology
  • Mice
  • RNA, Long Noncoding / biosynthesis
  • RNA, Long Noncoding / genetics
  • STAT3 Transcription Factor / drug effects
  • STAT3 Transcription Factor / genetics
  • Signal Transduction / drug effects
  • T-Lymphocytes / drug effects
  • Up-Regulation / drug effects

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • lnc-DC long non-coding RNA, human
  • Arsenic