Fig. 9

The combination of SAMHD1 silencing and radiotherapy promotes STING-IFN-I pathway activation in LUAD cells. SAMHD1 knockdown causes DNA end resection deficiency which impairs HR repair. SAMHD1 silencing collaborates with radiotherapy to induce ssDNA accumulation. The ssDNA fragments activate cytosolic DNA sensor IFI16. Then IFI16 activates STING. This triggers the phosphorylation of TBK1 and then the phosphorylation of IRF3. Thereby the p-IRF3 forms IRF3 homodimers that translocate into nucleus and results in the increased expression of IFN-I, including IFNβ, CCL5 and CXCL10