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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]

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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

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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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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:This SuperSeries is composed of the SubSeries listed below.

2021-08-23 | GSE163978 | GEO

Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

Project description:Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

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Evaporative cooling signals for wound healing in plants

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