Fig. 3
Mechanisms of DDRi and ICB affecting PD‐L1 expression and TME in tumors with DDR deficiency. DNA damage amplified by DDRi activates cGAS/STING, DNA damage response, and neoantigen pathway, inducing PD-L1 expression, pro-inflammatory cytokines release and CTLs infiltration while reducing Tregs and exhausted T cells, which combines with ICB, leading to immune activation and immunogenic cell death. Cyclic GMP‐AMP synthase (cGAS); stimulator of interferon genes (STING); double-strand breaks (DSB); homologous recombination (HR); microsatellite instability (MSI); mismatch repair deficiency (MMRd); homologous recombination deficiency (HRD); breast cancer 1/2 (BRCA1/2); DNA damage response (DDR); T cell receptor (TCR); programmed death‐ligand 1 (PD‐L1); programmed death‐1(PD-1); cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4); cytotoxic CD8+ T cells (CTLs); tumor-necrosis factorα (TNFα); interferon γ(IFN γ); interferon alpha/beta receptor (IFNAR); interferon regulatory factors (IRFs); regulatory T cells (Tregs); immune checkpoint blockade (ICB); granulocytic/monocytic myeloid-derived suppressor cells (g/mMDSCs); poly-ADP-ribose polymerase (PARP); ataxia telangiectasia and Rad3-related protein (ATR); checkpoint kinase 1 (CHK1); effector T-cells (Teff)