DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity.

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 effect is essential for priming of CD8⁺ T cells that mediate systemic tumour rejec

SUBMITTER: Vanpouille-Box C 

PROVIDER: S-EPMC5472757 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature