Targeting DNA-PKcs promotes anti-tumoral immunity via triggering cytosolic DNA sensing and inducing an inflamed tumor immuno-microenvironment in metastatic triple-negative breast cancer

Triple-negative breast cancer(TNBC)is highly malignant and refractory to immunotherapy through impeding the immune cell infiltration and inflammation in the tumor microenvi-ronment(TME).1 DNA-dependent protein kinase catalytic subunit(DNA-PKcs)is a member of the phosphatidylinositol 3-kinase-related kinase family,which is required for the non-homologous end joining repair.2 The effect of DNA-PKcs on the generation of cytosolic DNA and inflammation responsein tumor immuno-environment is not defined.We found a spe-cific DNA-PKcs inhibitor,NU7441,induced cytosolic DNA,stimulator of interferon genes(STING),and retinoic acid-inducible gene I(RIG-I)signals in vitro.