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TREX1 as a gate-keeper of cGAS/STING-mediated activation of interferon type I in cancer cells treated with DNA-damaging agents

Date

05 Mar 2018

Session

Novel immuno targets

Presenters

Sandra Demaria

Citation

Annals of Oncology (2018) 29 (suppl_3): iii1-iii6. 10.1093/annonc/mdy046

Authors

S. Demaria

Author affiliations

  • -, Weill Cornell Medical College, 10065 - New York/US
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Abstract 2

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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