The presence of DNA in the cytosol during viral infection elicits virus-specific immunity, a process orchestrated by the induction of interferon type I (IFN-I), which recruits and activates dendritic cells (DCs) capable of cross-priming CD8 T cell against viral antigens. Cytosolic double-stranded (ds)DNA is sensed by the cyclic GMP-AMP synthase (cGAS), which produces cGAMP and activates the downstream adaptor stimulator of IFN genes (STING) to induce IFN-I. CD8 T cells are also key anti-tumor effectors and their activation is largely dependent on the same pathways that regulate the activation of virus-specific CD8 T cells. Endogenous DNA accumulates in the cytosol of cells that harbor defects in the DNA damage repair (DDR) machinery, a common feature of neoplastic cells that can be exploited by DNA damaging chemotherapy and ionizing radiation (IR) to mimic a viral infection and activate cGAS/STING pathway in cancer cells.
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