Radiotherapy combined with immunotherapy: the dawn of cancer treatment

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

Published: July 29, 2022

Abstract Radiotherapy (RT) is delivered for purposes of local control, but can also exert systemic effect on remote and non-irradiated tumor deposits, which called abscopal effect. The view RT as a simple treatment has dramatically changed in recent years, it now widely accepted that provoke immune response gives strong rationale the combination immunotherapy (iRT). Nevertheless, several points remain to be addressed such interaction system, identification best schedules with (IO), expansion mechanism amplify iRT. To answer these crucial questions, we roundly summarize underlying showing whole landscape clinical trials attempt identify In consideration rarity effect, propose occurrence induced by radiation promoted 100% molecular genetic level. Furthermore, “radscopal effect” refers using low-dose reprogram microenvironment may overcome resistance Taken together, could regarded trigger antitumor response, help IO used radical added into current standard regimen patients metastatic cancer.

Language: Английский

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The Ca2+ sensor STIM1 regulates the type I interferon response by retaining the signaling adaptor STING at the endoplasmic reticulum

Nature Immunology, Journal Year: 2018, Volume and Issue: 20(2), P. 152 - 162

Published: Dec. 21, 2018

Language: Английский

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The interaction between ferroptosis and inflammatory signaling pathways

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(3)

Published: March 21, 2023

Abstract Ferroptosis is an iron-dependent regulated cell death driven by excessive lipid peroxidation. Inflammation one common and effective physiological event that protects against various stimuli to maintain tissue homeostasis. However, the dysregulation of inflammatory responses can cause imbalance immune system, dysfunction death. Recent studies have pointed out activation inflammation, including multiple inflammation-related signaling pathways, lead ferroptosis. Among related signal transduction we focused on five classical namely, JAK-STAT, NF-κB, inflammasome, cGAS-STING MAPK expounded their roles in To date, many agents shown therapeutic effects ferroptosis-related diseases modulating aforementioned pathways vivo vitro. Moreover, regulatory these iron metabolism peroxidation been described detail, contributing further understanding pathophysiological process Taken together, targeting inflammation will provide appropriate ways intervene ferroptosis diseases.

Language: Английский

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Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide

Clinical and Translational Medicine, Journal Year: 2020, Volume and Issue: 10(7)

Published: Nov. 1, 2020

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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The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?

Inflammation and Regeneration, Journal Year: 2022, Volume and Issue: 42(1)

Published: April 2, 2022

Abstract Cellular senescence is a state of irreversible cell cycle arrest that can be induced by variety potentially oncogenic stimuli, including DNA damage. Hence, has long been considered to suppress tumorigenesis, acting as guardian homeostasis. However, recent studies have revealed senescent cells exhibit the secretion series inflammatory cytokines, chemokines, growth factors, and matrix remodeling factors alter local tissue environment contribute chronic inflammation cancer. This phenotype termed senescence-associated secretory (SASP) observed not only in cultured vitro but also vivo . Recently, physiological pathological roles SASP increasingly clarified. Notably, several reported intrinsic mechanism factor production predominantly mediated through activation cGAS-STING (cyclic GMP-AMP synthase-stimulator interferon genes) pathway aberrantly accumulated fragments from nucleus cells. In contrast, various extrinsic triggers exist vivo, for example, induction hepatic stellate tumor microenvironment obesity-associated liver cancer translocated gut microbial metabolites. strategy elimination (senolysis) attracted increasing attention. Thus, role effects outcomes senolysis will discussed this review.

Language: Английский

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Lipotoxicity-induced mtDNA release promotes diabetic cardiomyopathy by activating the cGAS-STING pathway in obesity-related diabetes

Cell Biology and Toxicology, Journal Year: 2022, Volume and Issue: 39(1), P. 277 - 299

Published: March 2, 2022

Abstract Diabetic cardiomyopathy (DCM) is characterized by lipid accumulation, mitochondrial dysfunction, and aseptic inflammatory activation. Mitochondria-derived cytosolic DNA has been reported to induce inflammation activating cyclic GMP-AMP synthase (cGAS)/the stimulator of interferon genes (STING) pathway in the adipose, liver, kidney tissues. However, role mtDNA progression DCM unclear. In this study, with an obesity-related mouse model established feeding db/db mice a high-fat diet (HFD), we observed increased cytosol activated cGAS-STING signaling during DCM, as well downstream targets, IRF3, NF-κB, IL-18, IL-1β. further study palmitic acid (PA)-induced lipotoxic cell H9C2 cells, revealed that was result PA-induced overproduction ROS, which also led activation cGAS/STING system its targets. Notably, treatment extracted alone sufficient activate cultured cells. Besides, both knockdown STING cells inhibition C-176 injection could remarkably block apoptosis cardiomyocytes. conclusion, our elucidated critical mtDNA-induced pathogenesis provided preclinical validation for using inhibitor new potential therapeutic strategy DCM. Graphical abstract

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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cGAS–STING, an important signaling pathway in diseases and their therapy

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: March 23, 2024

Abstract Since cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism cGAS–STING past decade. Meanwhile, triggering transduction mechanisms have continuously illuminated. plays a key role human diseases, particularly DNA‐triggered inflammatory making it potentially effective therapeutic target for inflammation‐related diseases. Here, we aim summarize ancient origin defense mechanism, as well triggers, transduction, cGAS–STING. We will also focus on important roles signal under pathological conditions, such infections, cancers, autoimmune neurological visceral inflammations, review drug development targeting pathway. The main directions potential obstacles research diseases cancers be discussed. These advancements expand our understanding cGAS–STING, provide theoretical basis further exploration open up new strategies promising intervention multiple

Language: Английский

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Programmable Macrophage Vesicle Based Bionic Self‐Adjuvanting Vaccine for Immunization against Monkeypox Virus

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 8, 2024

The emergence of monkeypox has become a global health threat after the COVID-19 pandemic. Due to lack available specifically treatment against MPV, developing an vaccine is thus most prospective and urgent strategy. Herein, programmable macrophage vesicle based bionic self-adjuvanting (AM@AEvs-PB) first developed for defending virus (MPV). Based on MPV-related antigen-stimulated macrophage-derived vesicles, nanovaccine constructed by loading mature virion (MV)-related intracellular protein (A29L/M1R) simultaneously modifying with enveloped (EV) antigen (B6R), enabling them effectively promote presentation enhance adaptive immune through self-adjuvant Owing synergistic properties coloaded MV EV in defensing activation ratio antigen-presenting cells nearly four times than that single same dose, resulting stronger immunity host. Notably, intramuscular injection uptake AM@AEvs-PB demonstrated vigorous immune-protective effects mouse challenge attempt, offering promising strategy pre-clinical development.

Language: Английский

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