期刊
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
卷 9, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.828657
关键词
DNA damage; cGAS/STING; interferon; immune response; TME; remodeling; oncotherapy
资金
- National Natural Science Foundation of China [82071695, 82060535]
- Natural Science Foundation of Gansu Province [21JR7RA450]
- Innovation Fund of Higher Education of Gansu Province [2021B-010]
DNA damage plays a crucial role in tumorigenesis and development, and the cGAS/STING pathway is a key player in immune response. Recent studies have highlighted its significance in tumor immunotherapy and initiation/metastasis.
DNA damage occurs throughout tumorigenesis and development. The immunogenicity of DNA makes it an immune stimulatory molecule that initiates strong inflammatory responses. The cGAS/STING pathway has been investigated as a critical receptor in both exogenous and endogenous DNA sensing to activate the innate immune response. Growing lines of evidence have indicated that activation of the cGAS/STING pathway is critical in antitumor immunity. Recent studies have demonstrated the outstanding advancement of this pathway in tumor-combined immunotherapy; accordingly, increased studies focus on exploration of STING pathway agonists and analogues. However, current studies propose the potential use of the cGAS/STING pathway in tumor initiation and metastasis. Here, we review the molecular mechanisms and activation of the cGAS/STING pathway, and the relationship between DNA damage and this pathway, particularly highlighting the remodeling of immune contexture in tumor environment (TME) triggered by cascade inflammatory signals. A detailed understanding of TME reprogramming initiated by this pathway may pave the way for the development of new therapeutic strategies and rational clinical application.
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