The paradoxical role of radiation‐induced cGAS–STING signalling network in tumour immunity

XiaoYi Zhang; Han Zhang; Jiajia Zhang; Mengdie Yang; Mengqin Zhu; Yuzhen Yin; Xin Fan; Fei Yu

doi:10.1111/imm.13592

journal article Oct 25, 2022

The paradoxical role of radiation‐induced cGAS–STING signalling network in tumour immunity

XiaoYi Zhang

Han Zhang

Jiajia Zhang

Mengdie Yang Mengqin Zhu Yuzhen Yin Xin Fan

Fei Yu

Immunology Vol. 168 No. 3 pp. 375-388 · Wiley

View at Publisher Save 10.1111/imm.13592

Abstract

AbstractThe cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) pathway is an essential component of the innate immune system and is central to the identification of abnormal DNA leakage caused by ionising radiation (IR) damage. Cell‐intrinsic cGAS–STING initiation has been revealed to have tremendous potential for facilitating interferon synthesis and T‐cell priming. Targeting the cGAS–STING axis has been proposed as a strategy to improve radiosensitivity or enhance immunosurveillance. However, due to the complex biology of the irradiated tumour microenvironment and the extensive involvement of the cGAS–STING pathway in various physiological and pathological processes, many defects in this strategy limit the therapeutic effect. Here, we outline the molecular mechanisms by which IR activates the cGAS–STING pathway and analyse the dichotomous roles of the cGAS–STING pathway in modulating cancer immunity after radiotherapy (RT). Then, based on the crosstalk between the cGAS–STING pathway and other signalling events induced by IR, such as necroptosis, autophagy and other cellular effects, we discuss the immunomodulatory actions of the broad cGAS–STING signalling network in RT and their potential therapeutic applications. Finally, recent advances in combination therapeutic strategies targeting cGAS–STING in RT are explored.

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Details

Published: Oct 25, 2022
Vol/Issue: 168(3)
Pages: 375-388
License: View

Authors

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XiaoYi Zhang