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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE253593 | GEO | 2024/05/13

REPOSITORIES: GEO

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_mouse]

Project description:Dendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory DCs (mregDCs) suppress DC antigen cross-presentation while driving TH2 and regulatory T cell differentiation within tumor-draining lymph node tissues. Transcriptional and metabolic studies show that mregDC functionality is dependent upon the mevalonate biosynthetic pathway and the master transcription factor, SREBP2. Melanoma-derived lactate activates DC SREBP2 in the tumor microenvironment (TME) and drives mregDC development from conventional DCs. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promotes anti-tumor CD8+ T cell activation and suppresses melanoma progression. CD63+ mregDCs reside within the sentinel lymph nodes of melanoma patients. Collectively, this work describes a tumor-driven SREBP2-dependent program that promotes CD63+ mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_human]

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression

Project description:A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_mouse]

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [CITEseq]

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [scRNAseq_human]

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A Lactate-induced SREBF2-dependent genetic program drives an immunotolerant dendritic cell population during cancer progression [Spatial transcriptomics]

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