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Review
. 2023 Mar;168(3):375-388.
doi: 10.1111/imm.13592. Epub 2022 Oct 25.

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

Xiaoyi Zhang  1   2 , Han Zhang  1   2 , Jiajia Zhang  1   2 , Mengdie Yang  1   2 , Mengqin Zhu  1   2 , Yuzhen Yin  1   2 , Xin Fan  1   2 , Fei Yu  1   2
Affiliations
Free article
Review

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

Xiaoyi Zhang et al. Immunology. 2023 Mar.
Free article

Abstract

The 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.

Keywords: antitumour immunity; cGAS-STING; ionising radiation; tumour microenvironment; type I interferon.

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References

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