Nuclear PD-L1 triggers tumour-associated inflammation upon DNA damage.

ABSTRACT: Immune checkpoint inhibitors against PD-1/PD-L1 are highly effective in immunologically hot tumours such as triple-negative breast cancer, wherein constitutive DNA damage promotes inflammation, while inducing PD-L1 expression to avoid attack by cytotoxic T cells. However, whether and how PD-L1 regulates the DNA damage response and inflammation remains unclear. Here, we show that nuclear PD-L1 activates the ATR-Chk1 pathway and induces proinflammatory chemocytokines upon genotoxic stress. PD-L1 interacts with ATR and is essential for Chk1 activation and chromatin binding. cGAS-STING and NF-κB activation in the late phase of the DNA damage response is inhibited by PD-L1 deletion or by inhibitors of ATR and Chk1. Consequently, the induction of proinflammatory chemocytokines at this stage is i

SUBMITTER: Nihira NT 

PROVIDER: S-EPMC11811057 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature