Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade

ABSTRACT: Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade

PROVIDER: PRJNA1140232 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade

Project description:The potent immunostimulatory effects of toll-like receptor 8 (TLR8) agonism in combination with PD-1 blockade has resulted in a variety of preclinical investigations, yet the mechanism of action in humans remains unknown. We used scRNAsequencing and multi-spectral spatial imaging to elucidate the tumor immune microenvironment and correlates to response to a a unique open-label phase 1b pre-operative window of opportunity clinical trial (NCT03906526) in head and neck squamous cell carcinoma (HNSCC)

2024-08-14 | GSE273138 | GEO

Treatment of human monocytes with TLR7 or TLR8 agonists

Project description:Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors 3 deidentified donors from the Red Cross, monocytes from each donor incubated overnight with either vehicle, TLR7 agonist or TLR8 agonist

2014-12-24 | E-GEOD-64480 | biostudies-arrayexpress

Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2’O-methylation

Project description:Mechanistic studies have revealed that TLR8 senses single-stranded RNA (ssRNA) fragments, processed via synergistic cleavage by ribonucleases (RNase) T2 and RNase A family members. Processing by these RNases releases uridines and purine-terminated residues resulting in TLR8 activation. Monocytes show high expression of RNase 6, yet this RNase has not been analyzed for its physiological contribution to recognition of bacterial RNA by TLR8. Herein, we characterized molecular RNase 6 cleavage mechanisms. BLaER1 RNASE6-/- cells showed a dampened TLR8-dependent response upon stimulation with isolated bacterial RNA (bRNA) but also upon infection with live whole bacteria. Pretreatment of bacterial RNA with recombinant RNase 6 generated fragments that induced stimulation in RNASE6 knockout cells. 2’O-RNA methyl modification, when introduced at the first uridine in the UA dinucleotide, impaired upstream processing by RNase 6 and dampened TLR8 stimulation. In summary, this data shows that RNase 6 plays a critical role in the processing of bacterial RNA by generating uridine-terminated breakdown products that ultimately activate TLR8.

2024-09-12 | PXD053881 | Pride

STING is essential for TLR8 induced IFN

Project description:The innate immune system is equipped with multiple receptors to detect microbial nucleic acids and induce type I interferon (IFN) to restrict viral replication. When dysregulated these receptor pathways induce inflammation in response to host nucleic acids and promote development and persistence of autoimmune diseases like Systemic Lupus Erythematosus (SLE). IFN production is regulated by the Interferon Regulatory Factor (IRF) transcription factor family of proteins that function downstream of several innate immune receptors such as Toll-like receptors (TLRs) and Stimulator of Interferon Genes (STING). Although both TLRs and STING activate the same downstream molecules, the pathway by which TLRs and STING activate IFN response are thought to be independent. Here we show that STING plays a previously undescribed role in human TLR8 signaling. Stimulation with the TLR8 ligands induced IFN secretion in primary human monocytes, and inhibition of STING reduced IFN secretion from primary monocytes from 8 healthy donors. We demonstrate that TLR8-induced IRF activity was reduced by STING inhibitors. Moreover, TLR8-induced IRF activity was blocked by inhibition or loss of IKKε, but not TBK1. Bulk RNA transcriptomic analysis supported a model where TLR8 induces transcriptional responses associated with SLE that can be downregulated by inhibition of STING. These data demonstrate that STING is required for full TLR8-to-IRF signaling and provide evidence for a new framework of crosstalk between cytosolic and endosomal innate immune receptors, which could be leveraged to treat IFN driven autoimmune diseases.

2024-06-03 | GSE233450 | GEO

Reversal of human regulatory T cell suppression throgh TLR8 signaling

Project description:Analyses of gene alterations of human Treg cells treated with or without TLR8 ligand using the Illumina whole-genome Human HT-12 BeadChips. The study will provide important information for the molecular signature changes during the reversal of human Treg suppression mediated by activation of TLR8 signaling.

2018-12-30 | GSE118311 | GEO

Treatment of human monocytes with TLR7 or TLR8 agonists

Project description:Goal was to detect differences in response to TLR7 versus TLR8 agonists in human monocytes from healthy donors

2014-12-24 | GSE64480 | GEO

Quantitative Analysis of CXCL4 and TLR8 signaling crosstalk in human primary monocytes by RNA-Seq

Project description:To gain a comprehensive understanding of gene regulation in CXCL4 and TLR8 signaling crosstalk, we treated primary human blood monocytes with CXCL4 and TLR8 ssRNA ligand ORN8L for 6 h and performed transcriptomic analysis via RNA-seq. We observed that CXCL4 interacted with TLR8 ssRNA ligand and triggered inflammatory cytokine storm including IL6, IL12p40, TNF and IFNβ, and pro-fibrotic gene expression and activated NLRP3 inflammasome leading to interleukin-1β (IL-1β) secretion and pyroptosis in human blood monocytes.

2022-05-13 | GSE181889 | GEO

Distinct regulation of gene promoters and enhancers by CXCL4 and TLR8 in human CD14+ monocytes

2022-05-13 | GSE181886 | GEO

Nanoparticles-mediated TRPV1 channel blockade amplifies cancer thermo-immunotherapy via heat shock factor 1 modulation

Project description:Survival of malignant tumours is highly relevant to their intrinsic self-defense pathways such as heat shock protein (HSP) during cancer therapy, yet precisely dismantling self-defenses to amplify antitumour potency remains unexplored. Herein, we demonstrate that nanoparticles-mediated transient receptor potential vanilloid member 1 (TRPV1) channel blockade selectively modulates heat shock factor 1 to suppress dual self-defense pathways for potentiating thermo-immunotherapy. TRPV1 blockade is identified to inhibit calcium influx and subsequent nuclear translocation of HSF1 upon hyperthermia, leading to selective suppression of stressfully overexpressed HSP70 for enhancing thermotherapeutic efficacy against a variety of primary, metastatic and recurrent tumours. Particularly, the suppression of HSF1 translocation further restrains TGFβ pathway to apparently degrade extracellular matrix in tumour for improving the infiltration of antitumour therapeutics and immune cells into highly fibrotic and immunosuppressive pancreatic cancers, ultimately synergizing with anti-PD-L1 antibody to retrieve thermo-immunotherapy with tumour-eradicable and immune memory effects. The nanoparticles-mediated TRPV1 blockade represents as an effective and universal approach to selectively dismantle self-defenses for potent cancer therapy.

2022-03-24 | GSE199299 | GEO

RIPK3 negatively regulates the (CXCL4+TLR8)-induced IFN response while promoting NLRP3 inflammasome activation in human monocytes

Project description:To investigate the function of RIPK3 in regulation of IFN response and inflammatory response in human monocytes stimulated with CXCL4 and TLR8, We blocks (CXCL4 + TLR8)-induced pyroptosis and RIPK3 activation using necrosulfonamide (NSA, 5 µM) and GSK'872 (10 µM) and measure gene expression genome-wide with RNA-seq.

2023-04-30 | GSE201909 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data