The cGAS-STING pathway: a dual regulator of immune response in cancer and therapeutic implications
Abstract While the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway promotes anti-tumor immunity by detecting cytoplasmic DNA and inducing type I interferons, it also facilitates immune evasion through PD-L1 upregulation. Autophagy enhances cGAS signaling by delivering i...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-025-06843-2 |
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| Summary: | Abstract While the cyclic GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway promotes anti-tumor immunity by detecting cytoplasmic DNA and inducing type I interferons, it also facilitates immune evasion through PD-L1 upregulation. Autophagy enhances cGAS signaling by delivering it to autophagosomes, boosting DNA sensing, while phase separation into liquid droplets further amplifies its activity and regulates autophagy, affecting tumor proliferation. Oxidative stress and DNA damage activate cGAS-STING, triggering pro-inflammatory cytokines that drive chronic inflammation and metabolic disorders. Interactions with immune checkpoint inhibitors augment T cell responses against tumors, yet concurrent PD-L1 induction underscores a complex balance between activation and suppression. Therapeutic strategies—combining DNA damage response inhibitors with checkpoint blockade—show promise in amplifying antitumor immunity. Moreover, post-translational modifications, including m6A methylation and acetylation, fine-tune cGAS function and downstream signaling. Together, these insights reveal the dualistic nature of cGAS-STING in cancer, offering avenues for targeted interventions that leverage its immunostimulatory potential while mitigating mechanisms of immune escape. Additionally, cGAS-driven inflammation links to metabolic dysfunction and chronic disease, underscoring its broad clinical relevance. |
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| ISSN: | 1479-5876 |