Radiation with DNA-PK inhibition increased cytosolic dsDNA and tumoural type 1 IFN signalling in a cGAS- and STING-independent, but an RNA POL III, RIG-I, and MAVS-dependent manner. Triple combination with anti-PD-L1 potentiated anti-tumour immunity with a significant increase in the number of CD4+ , CD8+ , and Granzyme B+ cells compared to radiation alone or radiation with M3814. Here, GZMB is linked to neoplasm.