Base excision repair regulates PD-L1 expression in cancer cells

Oncogene. 2019 Jun;38(23):4452-4466. doi: 10.1038/s41388-019-0733-6. Epub 2019 Feb 12.


Programmed death-ligand 1 (PD-L1) is a key factor influencing cancer immunotherapy; however, the regulation of PD-L1 expression in cancer cells remains unclear, particularly regarding DNA damage, repair and its signalling. Herein, we demonstrate that oxidative DNA damage induced by exogenously applied hydrogen peroxide (H2O2) upregulates PD-L1 expression in cancer cells. Further, depletion of the base excision repair (BER) enzyme DNA glycosylase augments PD-L1 upregulation in response to H2O2. PD-L1 upregulation in BER-depleted cells requires ATR/Chk1 kinase activities, demonstrating that PD-L1 upregulation is mediated by DNA damage signalling. Further analysis of The Cancer Genome Atlas revealed that the expression of PD-L1 is negatively correlated with that of the BER/single-strand break repair (SSBR) and tumours with low BER/SSBR gene expression show high microsatellite instability and neoantigen production. Hence, these results suggest that PD-L1 expression is regulated in cancer cells via the DNA damage signalling and neoantigen-interferon-γ pathway under oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7-H1 Antigen / physiology*
  • Cell Line, Tumor
  • Checkpoint Kinase 1 / metabolism
  • DNA Damage*
  • DNA Glycosylases / metabolism
  • DNA Repair*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Immunotherapy
  • Interferon-gamma / metabolism
  • MCF-7 Cells
  • Microsatellite Repeats / genetics
  • Mutation
  • Neoplasms / genetics
  • Oxidative Stress
  • Oxygen / chemistry
  • Signal Transduction
  • Up-Regulation


  • B7-H1 Antigen
  • CD274 protein, human
  • Interferon-gamma
  • Hydrogen Peroxide
  • CHEK1 protein, human
  • Checkpoint Kinase 1
  • DNA Glycosylases
  • Oxygen