DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity
Cornell University · Weill Cornell Medicine · +6 more institutions
Abstract
Abstract Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12–18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-β by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-β production, resulting in recruitment and activation of Batf3-dependent dendritic cells. This…
Citation impact
- FWCI
- 60.00
- Percentile
- 100%
- References
- 41
Authors
10- CVClaire Vanpouille‐BoxCorresponding
Cornell University, Weill Cornell Medicine
- AAAmandine Alard
Université Toulouse III - Paul Sabatier, Inserm, Centre de Recherche en Cancérologie de Toulouse, New York University
- MJMolykutty J. Aryankalayil
National Cancer Institute, Center for Cancer Research
- YSYasmeen Sarfraz
Cornell University, Weill Cornell Medicine
- JMJulie M. Diamond
Cornell University, Weill Cornell Medicine
Topics & keywords
- Abscopal effect
- Context (archaeology)
- Immunogenicity
- Cancer research
- CD8
- Effector
- DNA damage
- Immunotherapy
- Good health and well-being
Funding
- UDU.S. Department of DefenseAwards: W81XWH-13-1-0012, W81XWH, W81XWH-13
- BCBreast Cancer Research FoundationAward: S10 RR027619
- CFChemotherapy Foundation
- YUYork University
- NINational Institutes of HealthAwards: TR000038, P30CA016087, R01 CA201246, W81XWH, CA201246, NIH R01, UL1 TR000038
- WCWeill Cornell Medical College
- NCNational Cancer InstituteAwards: R01 CA201246, P30CA016087