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

Trends in Immunology

Volumn 39, Issue 1, 2018, Pages 44-54

  Ng, Kevin W ^a,c   Marshall, Erin A ^a,c   Bell, John C ^b   Lam, Wan L ^a  

^a BRITISH COLUMBIA CANCER AGENCY   (Canada)

^b OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^c NONE

Author keywords

[No Author keywords available]

Indexed keywords

GENOMIC DNA; BLOCKING ANTIBODY; DNA; MB21D1 PROTEIN, HUMAN; MEMBRANE PROTEIN; MPYS PROTEIN, HUMAN; NUCLEOTIDYLTRANSFERASE; T LYMPHOCYTE RECEPTOR;

ADAPTIVE IMMUNITY; ANTIGEN PRESENTING CELL; CANCER CELL; CANCER GROWTH; CANCER SURVIVAL; CELL CYCLE ARREST; CELL INFILTRATION; CELL MATURATION; CELL PHAGOCYTOSIS; CGMP AMP SYNTHASE STIMULATOR OF INTERFERON GENE; DNA DAMAGE; GENE; GENE MUTATION; HUMAN; IMMUNE EVASION; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; IMMUNOMODULATION; INNATE IMMUNITY; MACROPHAGE; METASTASIS; ONCOLYTIC VIROTHERAPY; PREVALENCE; REVIEW; T LYMPHOCYTE ACTIVATION; TUMOR ESCAPE; TUMOR GROWTH; TUMOR IMMUNITY; TUMOR MICROENVIRONMENT; TUMOR VOLUME; UPREGULATION; ANIMAL; CARCINOGENESIS; IMMUNOLOGY; IMMUNOTHERAPY; INFLAMMATION; METABOLISM; NEOPLASM; PROCEDURES; SIGNAL TRANSDUCTION;

ANIMALS; ANTIBODIES, BLOCKING; CARCINOGENESIS; COSTIMULATORY AND INHIBITORY T-CELL RECEPTORS; DNA; HUMANS; IMMUNITY, INNATE; IMMUNOTHERAPY; INFLAMMATION; MEMBRANE PROTEINS; NEOPLASMS; NUCLEOTIDYLTRANSFERASES; SIGNAL TRANSDUCTION; TUMOR ESCAPE;

EID: 85027723272     PISSN: 14714906     EISSN: 14714981     Source Type: Journal    
DOI: 10.1016/j.it.2017.07.013     Document Type: Review

References (60)

1. Jamal-Hanjani, M., et al. Tumour heterogeneity and immune-modulation. Curr. Opin. Pharmacol. 13 (2013), 497–503.
2. van den Boorn, J.G., Hartmann, G., Turning tumors into vaccines: co-opting the innate immune system. Immunity 39 (2013), 27–37.
3. Grivennikov, S.I., et al. Immunity, inflammation, and cancer. Cell 140 (2010), 883–899.
4. Elinav, E., et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat. Rev. Cancer 13 (2013), 759–771.
5. Gajewski, T.F., Corrales, L., New perspectives on type I IFNs in cancer. Cytokine Growth Factor Rev. 26 (2015), 175–178.
6. Zitvogel, L., et al. Type I interferons in anticancer immunity. Nat. Rev. Immunol. 15 (2015), 405–414.
7. Schlee, M., Hartmann, G., Discriminating self from non-self in nucleic acid sensing. Nat. Rev. Immunol. 16 (2016), 566–580.
8. Barber, G.N., STING: infection, inflammation and cancer. Nat. Rev. Immunol. 15 (2015), 760–770.
9. Gray, E.E., et al. The AIM2-like receptors are dispensable for the interferon response to intracellular DNA. Immunity 45 (2016), 255–266.
10. Wu, J., et al. Cyclic GMP–AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science 339 (2013), 826–830.
11. Ablasser, A., et al. cGAS produces a 2′–5’-linked cyclic dinucleotide second messenger that activates STING. Nature 498 (2013), 380–384.
12. Sun, L., et al. Cyclic GMP–AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339 (2013), 786–791.
13. Ablasser, A., et al. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP. Nature 503 (2013), 530–534.
14. Bridgeman, A., et al. Viruses transfer the antiviral second messenger cGAMP between cells. Science 349 (2015), 1228–1232.
15. Gentili, M., et al. Transmission of innate immune signaling by packaging of cGAMP in viral particles. Science 349 (2015), 1232–1236.
16. Chen, Q., et al. Regulation and function of the cGAS–STING pathway of cytosolic DNA sensing. Nat. Immunol. 17 (2016), 1142–1149.
17. Woo, S.R., et al. STING-dependent cytosolic DNA sensing mediates innate immune recognition of immunogenic tumors. Immunity 41 (2014), 830–842.
18. Ho, S.S., et al. The DNA structure-specific endonuclease MUS81 mediates DNA sensor STING-dependent host rejection of prostate cancer cells. Immunity 44 (2016), 1177–1189.
19. Ahn, J., et al. Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun., 5, 2014, 5166.
20. Vanpouille-Box, C., et al. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat. Commun., 8, 2017, 15618.
21. Mackenzie, K.J., et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature, 2017, 10.1038/nature23449 Published online July 24, 2017.
22. Carroll, E.C., et al. The vaccine adjuvant chitosan promotes cellular immunity via DNA sensor cGAS–STING-dependent induction of type I interferons. Immunity 44 (2016), 597–608.
23. Xia, T., et al. Deregulation of STING signaling in colorectal carcinoma constrains DNA damage responses and correlates with tumorigenesis. Cell Rep. 14 (2016), 282–297.
24. Xia, T., et al. Recurrent loss of STING signaling in melanoma correlates with susceptibility to viral oncolysis. Cancer Res. 76 (2016), 6747–6759.
25. Demaria, O., et al. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity. Proc. Natl. Acad. Sci. U. S. A. 112 (2015), 15408–15413.
26. Deng, L., et al. STING-dependent cytosolic DNA sensing promotes radiation-induced type I interferon-dependent antitumor immunity in immunogenic tumors. Immunity 41 (2014), 843–852.
27. Ohkuri, T., et al. STING contributes to antiglioma immunity via triggering type I IFN signals in the tumor microenvironment. Cancer Immunol. Res 2 (2014), 1199–1208.
28. Li, T., et al. Antitumor activity of cGAMP via stimulation of cGAS–cGAMP–STING–IRF3 mediated innate immune response. Sci. Rep., 6, 2016, 19049.
29. Cerboni, S., et al. Intrinsic antiproliferative activity of the innate sensor STING in T lymphocytes. J. Exp. Med. 214 (2017), 1769–1785.
30. Larkin, B., et al. Cutting edge: activation of STING in T cells induces type I IFN responses and cell death. J. Immunol. 199 (2017), 397–402.
31. Corrales, L., et al. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11 (2015), 1018–1030.
32. Fu, J., et al. STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade. Sci. Transl. Med., 7, 2015, 283ra252.
33. Tang, C.H., et al. Agonist-mediated activation of STING induces apoptosis in malignant B cells. Cancer Res. 76 (2016), 2137–2152.
34. Hartlova, A., et al. DNA damage primes the type I interferon system via the cytosolic DNA sensor STING to promote anti-microbial innate immunity. Immunity 42 (2015), 332–343.
35. Luthra, P., et al. Topoisomerase II inhibitors induce DNA damage-dependent interferon responses circumventing Ebola virus immune evasion. MBio, 8, 2017 e00368–17.
36. Ching, L.M., et al. Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid. Br. J. Cancer 86 (2002), 1937–1942.
37. Roberts, Z.J., et al. IFN-β-dependent inhibition of tumor growth by the vascular disrupting agent 5, 6-dimethylxanthenone-4-acetic acid (DMXAA). J. Interferon Cytokine Res. 28 (2008), 133–139.
38. + T-cell-mediated antitumor immune response in murine models of lung cancer and mesothelioma. Cancer Res. 65 (2005), 11752–11761.
39. Lara, P.N. Jr, et al. Randomized Phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J. Clin. Oncol. 29 (2011), 2965–2971.
40. Conlon, J., et al. Mouse, but not human STING, binds and signals in response to the vascular disrupting agent 5,6-dimethylxanthenone-4-acetic acid. J. Immunol. 190 (2013), 5216–5225.
41. Yi, G., et al. Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides. PLoS One, 8, 2013, e77846.
42. Liu, X., et al. CD47 blockade triggers T cell-mediated destruction of immunogenic tumors. Nat. Med. 21 (2015), 1209–1215.
43. Wang, H., et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc. Natl. Acad. Sci. U. S. A. 114 (2017), 1637–1642.
44. Mori, A., et al. The vaccine adjuvant alum inhibits IL-12 by promoting PI3 kinase signaling while chitosan does not inhibit IL-12 and enhances Th1 and Th17 responses. Eur. J. Immunol. 42 (2012), 2709–2719.
45. Li, X.D., et al. Pivotal roles of cGAS–cGAMP signaling in antiviral defense and immune adjuvant effects. Science 341 (2013), 1390–1394.
46. Parker, Z.M., et al. Role of the DNA sensor STING in protection from lethal infection following corneal and intracerebral challenge with herpes simplex virus 1. J. Virol. 89 (2015), 11080–11091.
47. Kalamvoki, M., Roizman, B., HSV-1 degrades, stabilizes, requires, or is stung by STING depending on ICP0, the US3 protein kinase, and cell derivation. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), E611–E617.
48. Lam, E., et al. Adenovirus detection by the cGAS/STING/TBK1 DNA sensing cascade. J. Virol. 88 (2014), 974–981.
49. Anghelina, D., et al. Diminished innate antiviral response to adenovirus vectors in cGAS/STING-deficient mice minimally impacts adaptive immunity. J. Virol. 90 (2016), 5915–5927.
50. Lau, L., et al. DNA tumor virus oncogenes antagonize the cGAS–STING DNA-sensing pathway. Science 350 (2015), 568–571.
51. Dai, P., et al. Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing pathway. PLoS Pathog., 10, 2014, e1003989.
52. Hayes, J., et al. MicroRNAs in cancer: biomarkers, functions and therapy. Trends Mol. Med. 20 (2014), 460–469.
53. Liang, D., et al. Activated STING enhances Tregs infiltration in the HPV-related carcinogenesis of tongue squamous cells via the c-jun/CCL22 signal. Biochim. Biophys. Acta 1852 (2015), 2494–2503.
54. Ahn, J., et al. Diverse roles of STING-dependent signaling on the development of cancer. Oncogene 34 (2015), 5302–5308.
55. Lemos, H., et al. STING promotes the growth of tumors characterized by low antigenicity via IDO activation. Cancer Res. 76 (2016), 2076–2081.
56. Song, S., et al. Decreased expression of STING predicts poor prognosis in patients with gastric cancer. Sci. Rep., 7, 2017, 39858.
57. Huber, S., et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491 (2012), 259–263.
58. Munn, D.H., Mellor, A.L., IDO in the tumor microenvironment: inflammation, counter-regulation, and tolerance. Trends Immunol. 37 (2016), 193–207.
59. Chen, Q., et al. Carcinoma–astrocyte gap junctions promote brain metastasis by cGAMP transfer. Nature 533 (2016), 493–498.
60. Lichty, B.D., et al. Going viral with cancer immunotherapy. Nat. Rev. Cancer 14 (2014), 559–567.