cGAS-STING and Cancer: Dichotomous Roles in Tumor Immunity and Development

Trends Immunol. 2018 Jan;39(1):44-54. doi: 10.1016/j.it.2017.07.013. Epub 2017 Aug 19.

Abstract

cGMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) sensing has emerged as a key regulator of innate immune responses to both exogenous and endogenous DNA. Recent studies reveal critical roles for this pathway in natural antitumor immunity across cancer types as well as in immune checkpoint blockade therapy. However, it is also clear that some tumors evade cGAS-STING-mediated immune responses, and immunomodulatory therapeutics are currently being explored to target this pathway. Finally, we also discuss recent observations that cGAS-STING-mediated inflammation may promote tumor initiation, growth, and metastasis in certain malignancies and how this may complicate the utility of this pathway in therapeutic development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Blocking / therapeutic use*
  • Carcinogenesis
  • Costimulatory and Inhibitory T-Cell Receptors / immunology
  • DNA / immunology
  • Humans
  • Immunity, Innate
  • Immunotherapy / methods*
  • Inflammation
  • Membrane Proteins / metabolism*
  • Neoplasms / immunology*
  • Nucleotidyltransferases / metabolism*
  • Signal Transduction
  • Tumor Escape

Substances

  • Antibodies, Blocking
  • Costimulatory and Inhibitory T-Cell Receptors
  • Membrane Proteins
  • STING1 protein, human
  • DNA
  • Nucleotidyltransferases
  • cGAS protein, human

Grant support