1IN - TREX1 as a gate-keeper of cGAS/STING-mediated activation of interferon type I in cancer cells treated with DNA-damaging agents

Date 05 March 2018
Event TAT 2018 - Targeted Anticancer Therapies - Targeted Anticancer Therapies
Session Novel immuno targets
Topics Biomarkers
Translational Research
Presenter Sandra Demaria
Citation Annals of Oncology (2018) 29 (suppl_3): iii1-iii6. 10.1093/annonc/mdy046
Authors S. Demaria
  • -, Weill Cornell Medical College, 10065 - New York/US

Abstract

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.