Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMPSTING-IRF3 Mediated Innate Immune Response

作者：Li, Tiejun; Cheng, Hao; Yuan, Hong; Xu, Qiming; Shu, Chang; Zhang, Yuefan; Xu, Pengbiao; Tan, Jason; Rui, Yaocheng; Li, Pingwei; Tan, Xiangshi^*

来源：Scientific Reports, 2016, 6(1): 19049.

DOI：10.1038/srep19049

• CYCLIC GMP-AMP
• VASCULAR DISRUPTING AGENT
• DENDRITIC CELLS
• I INTERFERON
• IFN-GAMMA
• TUMOR MICROENVIRONMENT
• DNA SENSOR
• 2ND-MESSENGER
• DINUCLEOTIDE
• MECHANISM

Immunotherapy 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-beta, interferon-gamma, 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.

• 出版日期2016-1-12
• 单位复旦大学; 中国人民解放军第二军医大学