DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells

Nat Commun. 2017 Nov 24;8(1):1751. doi: 10.1038/s41467-017-01883-9.


Accumulating evidence suggests that exogenous cellular stress induces PD-L1 upregulation in cancer. A DNA double-strand break (DSB) is the most critical type of genotoxic stress, but the involvement of DSB repair in PD-L1 expression has not been investigated. Here we show that PD-L1 expression in cancer cells is upregulated in response to DSBs. This upregulation requires ATM/ATR/Chk1 kinases. Using an siRNA library targeting DSB repair genes, we discover that BRCA2 depletion enhances Chk1-dependent PD-L1 upregulation after X-rays or PARP inhibition. In addition, we show that Ku70/80 depletion substantially enhances PD-L1 upregulation after X-rays. The upregulation by Ku80 depletion requires Chk1 activation following DNA end-resection by Exonuclease 1. DSBs activate STAT1 and STAT3 signalling, and IRF1 is required for DSB-dependent PD-L1 upregulation. Thus, our findings reveal the involvement of DSB repair in PD-L1 expression and provide mechanistic insight into how PD-L1 expression is regulated after DSBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • BRCA2 Protein / genetics
  • BRCA2 Protein / metabolism
  • Cell Line, Tumor
  • Checkpoint Kinase 1 / genetics
  • Checkpoint Kinase 1 / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Repair*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism*


  • B7-H1 Antigen
  • BRCA2 Protein
  • CD274 protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Checkpoint Kinase 1