STING in tumors: a focus on non-innate immune pathways

Front Cell Dev Biol. 2023 Oct 25:11:1278461. doi: 10.3389/fcell.2023.1278461. eCollection 2023.


Cyclic GMP-AMP synthase (cGAS) and downstream stimulator of interferon genes (STING) are involved in mediating innate immunity by promoting the release of interferon and other inflammatory factors. Mitochondrial DNA (mtDNA) with a double-stranded structure has greater efficiency and sensitivity in being detected by DNA sensors and thus has an important role in the activation of the cGAS-STING pathway. Many previous findings suggest that the cGAS-STING pathway-mediated innate immune regulation is the most important aspect affecting tumor survival, not only in its anti-tumor role but also in shaping the immunosuppressive tumor microenvironment (TME) through a variety of pathways. However, recent studies have shown that STING regulation of non-immune pathways is equally profound and also involved in tumor cell progression. In this paper, we will focus on the non-innate immune system pathways, in which the cGAS-STING pathway also plays an important role in cancer.

Keywords: PD-L1; TME; cGAS-STING; extracellular vesicles; mtDNA.

Publication types

  • Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study research was funded by The National Natural Science Foundation of China (Grant No. 82273479 to LZ), The Research Fund of Jilin Provincial Science and Technology Department (Grant No. 20210204072YY to BG), and China-Japan Union Hospital and College of Basic Medical Sciences, Jilin University Union Project (Grant No. KYXZ2022JC05 to LZ).