Tetsuo Tani, Haritha Mathsyaraja, Marco Campisi, Ze-Hua Li, Koji Haratani, Caroline G Fahey, Keiichi Ota, Navin R Mahadevan, Yingxiao Shi, Shin Saito, Kei Mizuno, Tran C Thai, Nobunari Sasaki, Mizuki Homme, Choudhury Fabliha B Yusuf, Adam Kashishian, Jipsa Panchal, Min Wang, Benjamin J Wolf, Thanh U Barbie, Cloud P Paweletz, Prafulla C Gokhale, David Liu, Ravindra Uppaluri, Shunsuke Kitajima, Jennifer Cain, David A Barbie
A substantial fraction of cancers evade immune detection by silencing STING (Stimulator of Interferon Genes)-interferon (IFN) signaling. Therapeutic reactivation of this program via STING agonists, epigenetic or DNA damaging therapies can restore anti-tumor immunity in multiple pre-clinical models. Here we show that adaptive induction of three prime exonuclease 1 (TREX1) restrains STING-dependent nucleic acid sensing in cancer cells via its catalytic function in degrading cytosolic DNA. Cancer cell TREX1 expression is coordinately induced with STING by autocrine IFN and downstream STAT1, preventing signal amplification...
January 10, 2024: Cancer Discovery