Year: 2017
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Analysis of pseudo transcription formation following transcription remodeling leading to homologous recombination repair, Anti cancer specific immune response after carbon ion irradiation, Basic and clinical research for advanced cancer heavy ion radiotherapy and individualized treatment, G5866893089, Molecular mechanism of PD-L1 upregulation in cancer cells after DNA double-strand break repair pathway following irradiation, Regulation of radiation sensitivity by a pathway linking DNA repair with cell-cycle control, Elucidation of the mechanism leading to the initiation of transcription associated homologous recombination
OpenAlex ID: W2768434280