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A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

ABSTRACT: A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

PROVIDER: PRJNA688466 | ENA |

REPOSITORIES: ENA

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A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

Project description:A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

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A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells [BMDCs]

Project description:A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells [BMDCs]

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A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells [EGR1-KO]

Project description:A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells [EGR1-KO]

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A mechanism of cooling hot tumors: Lactate attenuates inflammation in dendritic cells.

Project description:Turning non-inflamed (cold) tumors into inflamed (hot) tumors is important for maximizing the effect of immune checkpoint inhibitors (ICIs) against malignancies. We showed that lactate, a product of the Warburg effect, inhibited the efficacy of ICIs and suppressed IL-12 p40 expression in dendritic cells (DCs) through reducing NF-κB p65, p50, and c-Rel DNA-binding activity to the IL-12 p40 promoter. Additionally, lactate promoted the expression of early growth response protein 1 (EGR1), whose expression was increased in human invasive melanoma compared with non-invasive melanoma. We also found that EGR1 interacts with serum response factor (SRF) and represses the expression of CD80 in DCs. These findings suggest that lactate and its induced EGR1 are key factors that turn hot tumors into cold tumors and may represent targets in cancer treatment with ICIs.

| S-EPMC8441070 | biostudies-literature

A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

Project description:The epigenetic status of H3K27Ac was comparable between Egr1 deficient and WT bone marrow-derived dendritic cells (BMDCs). We identified a region that suggested the interaction of EGR1 in the Cd80 promoter.

2021-08-23 | GSE164027 | GEO

A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-23 | GSE163978 | GEO

A mechanism of cooling hot tumors: lactate attenuates inflammation in dendritic cells [BMDCs]

Project description:Lactic acid (LA) accumulation in the tumour environment occurs as a result of the accelerated glucose metabolism in tumour cells, the so-called Warburg effect. Because TLR4 agonists are one of the damage-associated molecular patterns, which are important stimulators of dendritic cells in the tumour microenvironment, we assessed the effects of LA on the response to LPS, the TLR4 ligand.

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Identification of genes regulated by L-lactate and by DL-lactate in Lactobacillus plantarum

Project description:L. plantarum is known to possess an L-lactate inducible lactate racemase activity (Goffin et al. 2005. J. Bacteriol. 187:6750). In the present study, microarrays were used in order to identify all genes that are up-regulated by L-lactate, but not by a racemic mixture of D- and L-lactate. A mutant of L. plantarum NCIMB8826 deficient for NAD-dependent L-lactate activity (TF101; Ferain et al. 1994. 176:596), and thus producing no L-lactate, was grown in MRS medium at 28Â°C until mid-exponential phase (OD600nm 0.75). The culture was then divided into 3 sub-cultures. Optically pure sodium L-lactate (200 mM) was added to the first sub-culture (TF101 + L-lac 200 mM). An equimolar mixture of sodium D- and L-lactate (100 mM each) was added to the second sub-culture (TF101 + L/D-lac 200 mM). The third sub-culture was not treated (TF101; reference sample). The three sub-cultures were further incubated at 28Â°C for 1h30 (a time known to be sufficient for induction of lactate racemase activity by L-lactate). Cells were harvested by centrifugation. Microarray data were used ot identify genes that are specifically induced by L-lactate (comparison of TF101 with TF101 + L-lac 200 mM), but not by DL-lactate (comparison of TF101 with T101 + L/D-lac 200 mM). There are no biological replicates.

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2023-03-01 | E-MTAB-8567 | biostudies-arrayexpress

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