Roles of natural killer cells in immunity to cancer, and applications to immunotherapy

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(2), P. 90 - 105

Published: May 30, 2022

Language: Английский

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The cGAS–STING pathway and cancer

Nature Cancer, Journal Year: 2022, Volume and Issue: 3(12), P. 1452 - 1463

Published: Dec. 12, 2022

Language: Английский

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Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion

Immunity, Journal Year: 2020, Volume and Issue: 53(1), P. 115 - 126.e5

Published: July 1, 2020

Language: Английский

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Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(6), P. 5977 - 6039

Published: Feb. 2, 2022

The stimulator of interferon genes (STING) cellular signaling pathway is a promising target for cancer immunotherapy. Activation the intracellular STING protein triggers production multifaceted array immunostimulatory molecules, which, in proper context, can drive dendritic cell maturation, antitumor macrophage polarization, T priming and activation, natural killer vascular reprogramming, and/or death, resulting immune-mediated tumor elimination generation immune memory. Accordingly, there significant amount ongoing preclinical clinical research toward further understanding role surveillance as well development modulators strategy to stimulate immunity. Yet, efficacy agonists limited by many drug delivery pharmacological challenges. Depending on class agonist desired administration route, these may include poor stability, immunocellular toxicity, immune-related adverse events, or lymph node targeting retention, low uptake delivery, complex dependence magnitude kinetics signaling. This review provides concise summary pathway, highlighting recent biological developments, immunological consequences, implications delivery. also offers critical analysis an expanding arsenal chemical strategies that are being employed enhance efficacy, safety, utility lastly draws attention several opportunities therapeutic advancements.

Language: Английский

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Role of the cGAS–STING pathway in systemic and organ-specific diseases

Nature Reviews Nephrology, Journal Year: 2022, Volume and Issue: 18(9), P. 558 - 572

Published: June 22, 2022

Language: Английский

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The STING1 network regulates autophagy and cell death

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 2, 2021

Cell death and immune response are at the core of life. In past decades, endoplasmic reticulum (ER) protein STING1 (also known as STING or TMEM173) was found to play a fundamental role in production type I interferons (IFNs) pro-inflammatory cytokines DNA derived from invading microbial pathogens damaged hosts by activating multiple transcription factors. addition this well-known function infection, inflammation, immunity, emerging evidence suggests that STING1-dependent signaling network is implicated health disease regulating autophagic degradation various cell modalities (e.g., apoptosis, necroptosis, pyroptosis, ferroptosis, mitotic death, immunogenic [ICD]). Here, we outline latest advances our understanding mechanisms pathways autophagy which may shed light on new targets for therapeutic interventions.

Language: Английский

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Cytosolic DNA sensing by cGAS: regulation, function, and human diseases

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: April 30, 2021

Abstract Sensing invasive cytosolic DNA is an integral component of innate immunity. cGAS was identified in 2013 as the major sensor that binds dsDNA to catalyze synthesis a special asymmetric cyclic-dinucleotide, 2′3′-cGAMP, secondary messenger bind and activate STING for subsequent production type I interferons other immune-modulatory genes. Hyperactivation signaling contributes autoimmune diseases but serves adjuvant anticancer immune therapy. On hand, inactivation causes deficiency sense clear viral bacterial infection creates tumor-prone microenvironment facilitate tumor evasion surveillance. Thus, activation tightly controlled. In this review, we summarize up-to-date multilayers regulatory mechanisms governing activation, including pre- post-translational regulations, cGAS-binding proteins, additional regulators such ions small molecules. We will also reveal pathophysiological function its product cGAMP human diseases. hope provide review recent research advances biology cGAS-targeted therapies

Language: Английский

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Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles

Nature Nanotechnology, Journal Year: 2022, Volume and Issue: 17(8), P. 891 - 899

Published: May 30, 2022

Language: Английский

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Multifaceted functions of STING in human health and disease: from molecular mechanism to targeted strategy

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 23, 2022

Since the discovery of Stimulator Interferon Genes (STING) as an important pivot for cytosolic DNA sensation and interferon (IFN) induction, intensive efforts have been endeavored to clarify molecular mechanism its activation, physiological function a ubiquitously expressed protein, explore potential therapeutic target in wide range immune-related diseases. With orthodox ligand 2'3'-cyclic GMP-AMP (2'3'-cGAMP) upstream sensor 2'3'-cGAMP synthase (cGAS) be found, STING acquires central functionality best-studied signaling cascade, namely cGAS-STING-IFN pathway. However, recently updated research through structural research, genetic screening, biochemical assay greatly extends current knowledge biology. A second pocket was discovered transmembrane domain synthetic agonist. On downstream outputs, accumulating studies sketch primordial multifaceted roles beyond cytokine-inducing function, such autophagy, cell death, metabolic modulation, endoplasmic reticulum (ER) stress, RNA virus restriction. Furthermore, with expansion interactome, details trafficking also get clearer. After retrospecting brief history viral interference milestone events since STING, we present vivid panorama biology taking into account information, especially versatile outputs functions IFN induction. We summarize pathogenesis various diseases highlight development small-molecular compounds targeting disease treatment combination latest research. Finally, discuss open questions imperative answer.

Language: Английский

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Biochemistry, Cell Biology, and Pathophysiology of the Innate Immune cGAS–cGAMP–STING Pathway

Annual Review of Biochemistry, Journal Year: 2022, Volume and Issue: 91(1), P. 599 - 628

Published: March 15, 2022

In the decade since discovery of innate immune cyclic GMP-AMP synthase (cGAS)-2'3'-cyclic (cGAMP)-stimulator interferon genes (STING) pathway, its proper activation and dysregulation have been rapidly implicated in many aspects human disease. Understanding biochemical, cellular, regulatory mechanisms this pathway is critical to developing therapeutic strategies that either harness it boost defense or inhibit prevent unwanted inflammation. review, we first discuss how second messenger cGAMP synthesized by cGAS response double-stranded DNA cGAMP's subsequent cell-type-dependent STING signaling cascades with differential physiological consequences. We then review as an immunotransmitter mediates tightly controlled cell-cell communication being exported from producing cells imported into responding via cell-type-specific transporters. Finally, which thecGAS-cGAMP-STING responds different sources mislocalized pathogen defense, cancer, autoimmune diseases.

Language: Английский

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