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. 2016 Jan:77:245-7.
doi: 10.1016/j.cyto.2015.08.258. Epub 2015 Aug 24.

Endogenous and pharmacologic targeting of the STING pathway in cancer immunotherapy

Leticia Corrales  1 , Thomas F Gajewski  2
Affiliations

Endogenous and pharmacologic targeting of the STING pathway in cancer immunotherapy

Leticia Corrales et al. Cytokine. 2016 Jan.
No abstract available

Keywords: STING pathway; Tumor immunology; Type I IFN.

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Figures

Figure
Figure
Working model of innate immune sensing of tumors that leads to spontaneous T cell responses in vivo. The STING pathway is activated within intra-tumoral dendritic cells (DCs) by tumor-derived DNA. Recognition of cytosolic DNA by cyclic GMP-AMP (cGAMP) synthase (cGAS) leads to the generation of cGAMP, the endogenous ligand of STING (stimulator of interferon genes). Therapeutically, the STING pathway can be stimulated by direct STING agonists, when the compounds are injected into the tumor site. This results in the phosphorylation of tank-binding kinase 1 (TBK1) and the transcription factor interferon regulatory factor 3 (IRF3), which induces expression of the type I IFN genes. Type I IFN signaling in the BATF3 (basic leucine zipper transcription factor ATF-like 3)-lineage of DCs leads to antigen-specific T cell priming, generating spontaneous anti-tumor T cell responses in vivo. Recruitment of effector T cells into the tumor microenvironment is then facilitated by the release of CXCL9/10 chemokines from DCs and other cells at the tumor site. Successfully recruited activated T cells induce direct tumor cell killing, leading to measurable tumor shrinkage.
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References

    1. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–61. - PMC - PubMed
    1. Gajewski TF, Woo SR, Zha Y, Spaapen R, Zheng Y, Corrales L, et al. Cancer immunotherapy strategies based on overcoming barriers within the tumor microenvironment. Curr Opin Immunol. 2013;25:268–76. - PubMed
    1. Harlin H, Meng Y, Peterson AC, Zha Y, Tretiakova M, Slingluff C, et al. Chemokine expression in melanoma metastases associated with CD8+ T-cell recruitment. Cancer Res. 2009;69:3077–85. - PMC - PubMed
    1. Diamond MS, Kinder M, Matsushita H, Mashayekhi M, Dunn GP, Archambault JM, et al. Type I interferon is selectively required by dendritic cells for immune rejection of tumors. J Exp Med. 2011;208:1989–2003. - PMC - PubMed
    1. Fuertes MB, Kacha AK, Kline J, Woo SR, Kranz DM, Murphy KM, et al. Host type I IFN signals are required for antitumor CD8+ T cell responses through CD8{alpha}+ dendritic cells. J Exp Med. 2011;208:2005–16. - PMC - PubMed

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