Antitumor Activity of cGAMP via Stimulation of cGAS-cGAMP-STING-IRF3 Mediated Innate Immune Response. Academic Article uri icon

abstract

  • 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-, interferon-, 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.

published proceedings

  • Sci Rep

altmetric score

  • 16.25

author list (cited authors)

  • Li, T., Cheng, H., Yuan, H., Xu, Q., Shu, C., Zhang, Y., ... Tan, X.

citation count

  • 150

complete list of authors

  • Li, Tiejun||Cheng, Hao||Yuan, Hong||Xu, Qiming||Shu, Chang||Zhang, Yuefan||Xu, Pengbiao||Tan, Jason||Rui, Yaocheng||Li, Pingwei||Tan, Xiangshi

publication date

  • January 2016