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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE164027 | GEO | 2021/08/23

REPOSITORIES: GEO

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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.

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.

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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]

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Analysis of signaling moelculs induced by UNE-C1 treatment

Project description:To investigate the mechanism on stimulation of BMDCs by UNE-C1, we performed RNA-Seq after treating UNE-C1 on BMDCs. Genes related with pro-inflammation such as IL-6, iNOS, IL-12, CD40, CD80, and CD86 were increased by UNE-C1 treatment. KEGG pathway analysis was performed using top 100 up-regulated genes indcued by UNE-C1 and found out that genes related with Toll-like signaling pathway is up-regulated by UNE-C1.

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