cGAS-STING, an important pathway in cancer immunotherapy

J Hematol Oncol. 2020 Jun 22;13(1):81. doi: 10.1186/s13045-020-00916-z.

Abstract

Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.

Keywords: Cancer; Combined therapy; Immunotherapy; STING pathway; cGAS-STING.

Publication types

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

MeSH terms

  • Adenylyl Cyclases / physiology
  • Adjuvants, Immunologic
  • Animals
  • CTLA-4 Antigen / antagonists & inhibitors
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Clinical Trials as Topic
  • DNA / metabolism
  • DNA, Neoplasm / metabolism
  • Drug Screening Assays, Antitumor
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy*
  • Immunotherapy, Adoptive
  • Membrane Proteins / agonists*
  • Membrane Proteins / chemistry
  • Membrane Proteins / physiology
  • Mice
  • Neoplasm Proteins / agonists*
  • Neoplasm Proteins / chemistry
  • Neoplasm Proteins / physiology
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Nucleotides, Cyclic / physiology*
  • Oncolytic Virotherapy
  • Protein Multimerization
  • Signal Transduction / drug effects*
  • Therapies, Investigational

Substances

  • Adjuvants, Immunologic
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Cancer Vaccines
  • DNA, Neoplasm
  • Immune Checkpoint Inhibitors
  • Membrane Proteins
  • Neoplasm Proteins
  • Nucleotides, Cyclic
  • STING1 protein, human
  • cyclic guanosine monophosphate-adenosine monophosphate
  • DNA
  • Adenylyl Cyclases