• Tiejun Li, Hao Cheng, Hong Yuan, Qiming Xu, Chang Shu, Yuefan Zhang, Pengbiao Xu, Jason Tan, Yaocheng Rui, Pingwei Li, and Xiangshi Tan.
• Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, 200433, China.
• Sci Rep. 2016 Jan 12; 6: 19049.

AbstractImmunotherapy is one of the key strategies for cancer treatment. The cGAS-cGAMP-STING-IRF3 pathway of cytosolic DNA sensing plays a pivotal role in antiviral defense. We report that the STING activator cGAMP possesses significant antitumor activity in mice by triggering the STING-dependent pathway directly. cGAMP enhances innate immune responses by inducing production of cytokines such as interferon-β, interferon-γ, and stimulating dendritic cells activation, which induces the cross-priming of CD8(+) T cells. The antitumor mechanism of cGAMP was verified by STING and IRF3, which were up-regulated upon cGAMP treatment. STING-deficiency dramatically reduced the antitumor effect of cGAMP. Furthermore, cGAMP improved the antitumor activity of 5-FU, and clearly reduced the toxicity of 5-FU. These results demonstrated that cGAMP is a novel antitumor agent and has potential applications in cancer immunotherapy.

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