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

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…

• TS
  Takeda Science Foundation
• CS
  Cell Science Research Foundation
• MO
  Ministry of Education, Culture, Sports, Science and Technology
• DS
  Daiichi Sankyo Foundation of Life Science
• JS
  Japan Society for the Promotion of Science

  Awards: JP17H04713, JP17K16420, JP26701005
• DS
  Daiichi Sankyo Europe