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Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain

ABSTRACT: Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain

PROVIDER: PRJNA805239 | ENA |

REPOSITORIES: ENA

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Intralesional TLR4 agonist treatment strengthens the organ defense against colonizing cancer cells in the brain

Project description:Brain metastasis in breast cancer remains difficult to treat and its incidence is increasing. Therefore, the development of new therapies is of utmost clinical relevance. Recently, toll-like receptor (TLR) 4 was correlated with IL6 expression and poor prognosis in 1 215 breast cancer primaries. In contrast, we demonstrated that TLR4 stimulation reduces microglia-assisted breast cancer cell invasion. However, the expression, prognostic value, or therapeutic potential of TLR signaling in breast cancer brain metastasis have not been investigated. We thus tested the prognostic value of various TLRs in two brain-metastasis gene sets. Furthermore, we investigated different TLR agonists, as well as MyD88 and TRIF-deficient microenvironments in organotypic brain-slice ex vivo co- cultures and in vivo colonization experiments. These experiments underline the ambiguous roles of TLR4, its adapter MyD88, and the target nitric oxide (NO) during brain colonization. Moreover, analysis of the gene expression datasets of breast cancer brain metastasis patients revealed associations of TLR1 and IL6 with poor overall survival. Finally, our finding that a single LPS application at the onset of colonization shapes the later microglia/macrophage reaction at the macro-metastasis brain-parenchyma interface (MMPI) and reduces metastatic infiltration into the brain parenchyma may prove useful in immunotherapeutic considerations.

2022-12-04 | GSE196519 | GEO

Study of Intratumoral Ipilimumab and TLR4 Agonist GLA-SE in Combination With Systemic Nivolumab and Chemotherapy

Project description:To determine the maximum tolerated dose (MTD), the recommended phase 2 dose (RP2D) and the toxicity profile (NCI CTCAE v5.0 and immune related adverse events) of i.t. administration of anti-CTLA4 antibody (ipilimumab) and TLR4 agonist (synthetic glucopyranosyl lipid A formulated in a stable emulsion [GLA-SE]) in colorectal LM (CRLM) in combination with intravenous (i.v.) administration of anti-PD-1 antibody (nivolumab) and chemotherapy (FOLFOX regimen).

| 2308023 | ecrin-mdr-crc

Intratumoral injection of TLR4 agonist GLA in A20 tumor model

Project description:The goal of this study was to investigate the effect of intratumoral injection of GLA-SE, a TLR4 agonist in stable emulsion (SE), in Balb/c mice with established A20 lymphoma.

2020-08-04 | GSE150457 | GEO

Intratumoral injection of TLR4 agonist GLA in A20 tumor model

Project description:Intratumoral injection of TLR4 agonist GLA in A20 tumor model

| PRJNA632482 | ENA

Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity

Project description:Immunoresponsive Gene 1 Facilitates TLR4-agonist-Induced Augmentation of Innate Antimicrobial Immunity

| PRJNA1168170 | ENA

Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A

Project description:Toll-like receptor (TLR)4 agonists are known potent immunostimulatory compounds. These compounds can be formulated as part of novel adjuvants to enhance vaccine medicated immune responses. However, the contribution of the formulation to the innate in vivo activity of TLR4 agonist compounds is not well understood. Molecular expression profiles and cellular responses in a mouse model were used to compare for GLA-SE, GLA, Alum, SE, PBS. This study was to evaluate the mechanism of actions of different adjuvants and to identify potential biomarkers for clinical evaluation.

2013-01-09 | GSE43373 | GEO

Molecular and cellular response profiles induced by the TLR4 agonist-based adjuvant Glucopyranosyl Lipid A

2013-01-09 | E-GEOD-43373 | biostudies-arrayexpress

Transcriptome response after addition of individual agonists of TLR4 (MPLA) and NOD2 (MDP) receptors to THP-1 cells or its combination

2016-04-05 | GSE79900 | GEO

Transcriptome response after addition of individual agonists of TLR4 (MPLA) and NOD2 (MDP) receptors to THP-1 cells or its combination

Project description:Using microarray analysis, we explored the differences in gene expression profiles between individual and combined stimulation of Toll-like receptor 4 (TLR4) and Nucleotide oligomerization domain (NOD)-like receptor (NOD2) in THP-1 cells. Analysis was performed 3 hours post addition of TLR4 agonist MPLA and the NOD2 agonist MDP to THP-1 cells. The results provide the detailed molecular profile of the the genetic response to individual and combined stimulation of TLR4 and NOD2 receptors THP-1 cells (Invivogen) were seeded in 3-cm culture dishes at 1x10^6 cells per dish in RPMI medium. Next day, cells were treated with MDP (20Î¼g/ml) and MPLA (1Î¼g/ml) individually or in combination or left untreated.

2016-04-05 | E-GEOD-79900 | biostudies-arrayexpress

RNAseq of TLR agonist and SLE Immune complex stimulated SLE patient PBMCs with and without depletion of pDCs with CSL362

Project description:Stimulation experiments were done with PBMC from SLE or healthy donors treated with CSL362 or isotype control before stimulation with various stimuli including the TLR9 agonist 0.25 μM CpGc; the TLR4 agonist 10 μg/ml LPS; and the TLR3 agonist 10 μg/ml POLY I:C. As well as the SLE specific stimuli SLE immunoglobulin (Ig) + necrotic cell lysates (NCL) to form immune complexes; control healthy donor Ig + NCL; and SLE sera + NCL; or healthy donor sera + NCL to understand the specific effects of pDC depletion on different inducible gene transcripts.

2023-06-19 | GSE231686 | GEO

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