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

Cell Reports, Год журнала: 2015, Номер 11(7), С. 1018 - 1030

Опубликована: Май 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.

Язык: Английский

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Mitotic progression following DNA damage enables pattern recognition within micronuclei

Nature, Год журнала: 2017, Номер 548(7668), С. 466 - 470

Опубликована: Июль 28, 2017

Язык: Английский

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Tumour-intrinsic resistance to immune checkpoint blockade

Nature reviews. Immunology, Год журнала: 2019, Номер 20(1), С. 25 - 39

Опубликована: Сен. 30, 2019

Язык: Английский

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STING: infection, inflammation and cancer

Nature reviews. Immunology, Год журнала: 2015, Номер 15(12), С. 760 - 770

Опубликована: Ноя. 25, 2015

Язык: Английский

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Type I interferons in anticancer immunity

Nature reviews. Immunology, Год журнала: 2015, Номер 15(7), С. 405 - 414

Опубликована: Июнь 1, 2015

Язык: Английский

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

Nature Reviews Genetics, Год журнала: 2019, Номер 20(11), С. 657 - 674

Опубликована: Июль 29, 2019

Язык: Английский

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Small-cell lung cancer

Nature Reviews Disease Primers, Год журнала: 2021, Номер 7(1)

Опубликована: Янв. 14, 2021

Язык: Английский

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

The Journal of Experimental Medicine, Год журнала: 2018, Номер 215(5), С. 1287 - 1299

Опубликована: Апрель 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.

Язык: Английский

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Innate immune sensing of cytosolic chromatin fragments through cGAS promotes senescence

Nature Cell Biology, Год журнала: 2017, Номер 19(9), С. 1061 - 1070

Опубликована: Июль 31, 2017

Язык: Английский

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

Immunity, Год журнала: 2016, Номер 44(6), С. 1255 - 1269

Опубликована: Июнь 1, 2016

Язык: Английский

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