STING (or SRC) Like an ICB: Priming the Immune Response in Pancreatic Cancer

Cancer Research
Stanley I Gutiontov, Ralph R Weichselbaum

Abstract

Pancreatic adenocarcinoma is associated with a poor prognosis and resistance to immune checkpoint blockade. Zhang and colleagues demonstrate that inhibiting DNA repair by pharmacologic blockade or siRNA silencing of ataxia telangiectasia mutated (ATM) increases type I IFN release via a cGAS/STING-independent, SRC-dependent mechanism in models of pancreatic cancer. Furthermore, combining ATM inhibition and radiotherapy amplifies type I IFN signaling, increases programmed death ligand 1 (PD-L1) expression, tumor CD8+ T cells, and proinflammatory tumor macrophages. Finally, the combination of ATM silencing, radiotherapy, and PD-L1 blockade markedly improves in vivo murine tumor responses, supporting further investigation of this promising approach in pancreatic adenocarcinoma.See related article by Zhang et al., p. 3940.

References

Dec 15, 2000·Oncogene·R B Irby, T J Yeatman
Jun 5, 2012·The New England Journal of Medicine·Julie R BrahmerJon M Wigginton
Dec 23, 2016·Cancer Discovery·Jessica S BrownTimothy A Yap
Apr 18, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Martin WartenbergEva Karamitopoulou
Mar 14, 2019·Journal of the National Comprehensive Cancer Network : JNCCN·Margaret A TemperoGriselda Zuccarino-Catania

❮ Previous
Next ❯

Citations

Feb 17, 2020·NAR Cancer·Christian BaillyBruno Quesnel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Related Papers

Journal of Paediatrics and Child Health
Nicholas Jc SmithPadraic Grattan-Smith
The EMBO Journal
Amit Anand, Toshie Kai
The American Journal of Gastroenterology
Y BackesLeon M G Moons
© 2021 Meta ULC. All rights reserved