Direct Activation of STING in the Tumor Microenvironment Leads to Potent and Systemic Tumor Regression and Immunity

Cell Reports, Journal Year: 2015, Volume and Issue: 11(7), P. 1018 - 1030

Published: May 1, 2015

Spontaneous tumor-initiated T cell priming is dependent on IFN-β production by tumor-resident dendritic cells. On the basis of recent observations indicating that expression was upon activation host STING pathway, we hypothesized direct engagement through intratumoral (IT) administration specific agonists would result in effective anti-tumor therapy. After proof-of-principle studies using mouse agonist DMXAA showed a potent therapeutic effect, generated synthetic cyclic dinucleotide (CDN) derivatives activated all human alleles as well murine STING. IT injection induced profound regression established tumors mice and substantial systemic immune responses capable rejecting distant metastases providing long-lived immunologic memory. Synthetic CDNs have high translational potential cancer therapeutic.

Language: Английский

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Mitotic progression following DNA damage enables pattern recognition within micronuclei

Nature, Journal Year: 2017, Volume and Issue: 548(7668), P. 466 - 470

Published: July 28, 2017

Language: Английский

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Tumour-intrinsic resistance to immune checkpoint blockade

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 25 - 39

Published: Sept. 30, 2019

Language: Английский

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STING: infection, inflammation and cancer

Nature reviews. Immunology, Journal Year: 2015, Volume and Issue: 15(12), P. 760 - 770

Published: Nov. 25, 2015

Language: Английский

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Type I interferons in anticancer immunity

Nature reviews. Immunology, Journal Year: 2015, Volume and Issue: 15(7), P. 405 - 414

Published: June 1, 2015

Language: Английский

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DNA sensing by the cGAS–STING pathway in health and disease

Nature Reviews Genetics, Journal Year: 2019, Volume and Issue: 20(11), P. 657 - 674

Published: July 29, 2019

Language: Английский

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Small-cell lung cancer

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: Jan. 14, 2021

Language: Английский

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The cGAS–cGAMP–STING pathway connects DNA damage to inflammation, senescence, and cancer

The Journal of Experimental Medicine, Journal Year: 2018, Volume and Issue: 215(5), P. 1287 - 1299

Published: April 5, 2018

Detection of microbial DNA is an evolutionarily conserved mechanism that alerts the host immune system to mount a defense response infections. However, this detection also poses challenge as how distinguish foreign from abundant self-DNA. Cyclic guanosine monophosphate (GMP)-adenosine (AMP) synthase (cGAS) sensor triggers innate responses through production second messenger cyclic GMP-AMP (cGAMP), which binds and activates adaptor protein STING. cGAS can be activated by double-stranded irrespective sequence, including Although normally kept inactive in cells still not well understood, recent research has provided strong evidence genomic damage leads activation stimulate inflammatory responses. This review summarizes findings on instability trigger serves link inflammation, cellular senescence, cancer.

Language: Английский

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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

Nature Cell Biology, Journal Year: 2017, Volume and Issue: 19(9), P. 1061 - 1070

Published: July 31, 2017

Language: Английский

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Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors

Immunity, Journal Year: 2016, Volume and Issue: 44(6), P. 1255 - 1269

Published: June 1, 2016

Language: Английский

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