JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression

Cancers, Год журнала: 2019, Номер 11(12), С. 2002 - 2002

Опубликована: Дек. 12, 2019

Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling mediates almost all immune regulatory processes, including those that are involved in tumor cell recognition tumor-driven escape. Antitumor responses largely driven by STAT1 STAT2 induction type I II interferons (IFNs) the downstream programs IFNs potentiate. Conversely, STAT3 has been widely linked to cancer survival, immunosuppression, sustained inflammation microenvironment. The discovery JAK-STAT cross-regulatory mechanisms, post-translational control, non-canonical signal transduction added a new level complexity governance over initiation progression. Endeavors better understand vast effects on antitumor immunity have unearthed wide range targets, oncogenes, miRNAs, other co-regulatory factors, which direct specific phenotypical outcomes subsequent stimulation. Yet, rapidly expanding field therapeutic developments aimed resolve aberrations commonly reported multitude cancers marred off-target effects. Here, we discuss biology context cancer, consequences pathway perturbations current interventions, provide insight consideration for future targeting innovations.

Язык: Английский

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The role of interleukin-1 in general pathology

Inflammation and Regeneration, Год журнала: 2019, Номер 39(1)

Опубликована: Июнь 5, 2019

Interleukin-1, an inflammatory cytokine, is considered to have diverse physiological functions and pathological significances play important role in health disease. In this decade, interleukin-1 family members been expanding evidence accumulating that highlights the importance of linking innate immunity with a broad spectrum diseases beyond diseases. review, we look back on definition "inflammation" traditional general pathology discuss new insights into view its history molecular bases diseases, as well current progress therapeutics.

Язык: Английский

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Tumor Cell–Derived IL1β Promotes Desmoplasia and Immune Suppression in Pancreatic Cancer

Cancer Research, Год журнала: 2020, Номер 80(5), С. 1088 - 1101

Опубликована: Янв. 8, 2020

Pancreatic ductal adenocarcinoma (PDA) is an aggressive malignancy typified by a highly stromal and weakly immunogenic tumor microenvironment that promotes evolution contributes to therapeutic resistance. Here, we demonstrate PDA cell-derived proinflammatory cytokine IL1β essential for the establishment of protumorigenic microenvironment. Tumor promoted activation secretory phenotype quiescent pancreatic stellate cells established immunosuppressive milieu mediated M2 macrophages, myeloid-derived suppressor cells, CD1dhiCD5+ regulatory B Th17 cells. Loss IL1 signaling in stroma enabled intratumoral infiltration CD8+ cytotoxic T attenuated growth neoplasia, conferred survival advantage PDA-bearing mice. Accordingly, antibody-mediated neutralization significantly enhanced antitumor activity α-PD-1 was accompanied increased cell expression vivo driven microbial-dependent toll-like receptor 4 (TLR4) subsequent engagement NLRP3 inflammasome. Collectively, these findings identify hitherto unappreciated role orchestrating immune-modulatory program supports tumorigenesis. SIGNIFICANCE: These new modality immune evasion depends on production through TLR4-NLRP3 inflammasome activation. Targeting this axis might provide effective strategy.

Язык: Английский

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IL-1 Family Members in Cancer; Two Sides to Every Story

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Июнь 7, 2019

The IL-1 family of cytokines currently comprises seven ligands with pro-inflammatory activity (IL-1α and IL-1β, IL-18, IL-33, IL-36α, IL-36β, IL-36γ) as well two anti-inflammatory (IL-37, IL-38). These are known to play a key role in modulating both the innate adaptive immunes response, dysregulation linked variety autoimmune inflammatory diseases. Given increasing appreciation link between inflammation cancer, several members this pathogenesis cancer has been extensively investigated. In review, we highlight pro- anti-tumorigenic effects identified for almost all family, explore potential underlying mechanisms accounting these divergent effects. Such dual functions need be carefully assessed when developing therapeutic intervention strategies targeting cancer.

Язык: Английский

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Interleukin-1β and Cancer

Cancers, Год журнала: 2020, Номер 12(7), С. 1791 - 1791

Опубликована: Июль 4, 2020

Within a tumor, IL-1β is produced and secreted by various cell types, such as immune cells, fibroblasts, or cancer cells. The IL1B gene induced after “priming” of the cells second signal required to allow maturation inflammasome-activated caspase-1. then released leads transcription target genes through its ligation with IL-1R1 on expression are guided polymorphisms cellular context. In cancer, has pleiotropic effects angiogenesis, proliferation, migration, metastasis. Moreover, anti-cancer treatments able promote production opposite progression. This raises question whether not use inhibitors in treatment.

Язык: Английский

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Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA)

Cancers, Год журнала: 2019, Номер 12(1), С. 37 - 37

Опубликована: Дек. 21, 2019

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis treatment ADC SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with histological subtypes NSCLC. The present study aims key dysregulated pathways genes involved development relate them clinical traits. transcriptional changes between tumour normal tissues were investigated by RNA-seq. Gene ontology (GO), canonical analysis prediction upstream regulators, weighted gene co-expression network (WGCNA) co-expressed modules hub used explore biological functions identified genes. It was indicated that specific signatures differed significantly related distinct pathways. Of modules, four two most features SCC, respectively. CTLA4, MZB1, NIP7, BUB1B ADC, as well GNG11 CCNB2 are novel top size, SUVmax, recurrence-free survival. Our research provides more effective understanding importance relationships major NSCLC perspective searching for new molecular targets.

Язык: Английский

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Pyroptosis, metabolism, and tumor immune microenvironment

Clinical and Translational Medicine, Год журнала: 2021, Номер 11(8)

Опубликована: Авг. 1, 2021

Язык: Английский

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Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review

International Journal of Oral Science, Год журнала: 2020, Номер 12(1)

Опубликована: Янв. 2, 2020

Abstract Interleukin(IL)-1β, a pro-inflammatory cytokine, was elevated and participates in periodontitis. Not only the link between IL-1β periodontitis proved by clinical evidence, but also increased triggers series of inflammatory reactions promotes bone resorption. Currently, blockage has been therapeutic strategies for autoimmune autoinflammatory diseases such as rheumatoid arthritis, cryopyrin-associated periodic syndromes, gout type II diabetes mellitus. It is speculated that be potential target The review focuses on production, mechanism, present treatments future

Язык: Английский

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Breast cancer models: Engineering the tumor microenvironment

Acta Biomaterialia, Год журнала: 2020, Номер 106, С. 1 - 21

Опубликована: Фев. 9, 2020

Язык: Английский

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RhoA as a Key Regulator of Innate and Adaptive Immunity

Cells, Год журнала: 2019, Номер 8(7), С. 733 - 733

Опубликована: Июль 17, 2019

RhoA is a ubiquitously expressed cytoplasmic protein that belongs to the family of small GTPases. acts as molecular switch activated in response binding chemokines, cytokines, and growth factors, via mDia ROCK signaling cascade regulates activation cytoskeletal proteins, other factors. This review aims summarize our current knowledge on role general key regulator immune cell differentiation function. The contribution for primary functions innate types, namely neutrophils, macrophages, conventional dendritic cells (DC) (i) get by pathogen-derived endogenous danger signals, (ii) migrate sites infection inflammation, (iii) internalize pathogens has been fairly established. In DC, which constitute most potent antigen-presenting system, also important presentation antigen formation an immunological synapse between DC antigen-specific T prerequisite induce adaptive responses. B effector system Rho pivotal migration. More recently, mutations Rho-modulating factors have identified predispose autoimmune diseases causative hematopoietic malignancies.

Язык: Английский

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