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cGAS-STING Activation in the Tumor Microenvironment and Its Role in Cancer Immunity

  • Geneviève Pépin
  • Michael P. Gantier
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1024)

Abstract

Stimulator of interferon (IFN) genes (STING) is a key mediator in the immune response to cytoplasmic DNA sensed by cyclic GMP-AMP (cGAMP) synthase (cGAS). After synthesis by cGAS, cGAMP acts as a second messenger activating STING in the cell harboring cytoplasmic DNA but also in adjacent cells through gap junction transfer. While the role of the cGAS-STING pathway in pathogen detection is now well established, its importance in cancer immunity has only recently started to emerge. Nonetheless, STING appears to be an essential component in the recruitment of immune cells to the tumor microenvironment, which is paramount to immune clearance of the tumor. This review presents an overview of the growing literature around the role of the cGAS-STING pathway in the tumor microenvironment, with a specific focus on the role that cancer cells may play in the direct activation of this pathway, and its amplification through cell-cell transfer of cGAMP.

Keywords

cGAS cGAMP STING Interferon Connexin Cancer 

Notes

Acknowledgment

We thank Rebecca Smith, Jonathan Ferrand, and Lise Boursinhac for the assistance in the preparation of the manuscript. This work was funded in part by the Australian NHMRC (1062683 and 1081167 to M.P.G.), the Australian Research Council (140100594 Future Fellowship to M.P.G.), and the Victorian Government’s Operational Infrastructure Support Program. G.P. is a fellow from Fonds de Recherche du Québec – Santé (FRQS), Canada (35071).

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Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  1. 1.Centre for Innate Immunity and Infectious DiseasesHudson Institute of Medical ResearchClaytonAustralia
  2. 2.Department of Molecular and Translational ScienceMonash UniversityClaytonAustralia

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