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Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.

ABSTRACT: Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.

PROVIDER: PRJNA1064023 | ENA |

REPOSITORIES: ENA

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Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [scRNA-seq]

Project description:Tumour-host immune interactions lead to complex changes in the tumour microenvironment (TME), impacting progression, metastasis and response to therapy. While it is clear that cancer cells can have the capacity to alter immune landscapes, our understanding of this process is incomplete. Herein we show that endocytic trafficking at the plasma membrane, mediated by the small GTPase ARF6, enables melanoma cells to impose an immunosuppressive TME that accelerates tumour development. This ARF6-dependent TME is vulnerable to immune checkpoint blockade therapy (ICB) but in murine melanoma, loss of Arf6 causes resistance to ICB. Likewise, downregulation of ARF6 in patient tumours correlates with inferior overall survival after ICB. Mechanistically, these phenotypes are at least partially explained by ARF6-dependent recycling, which controls plasma membrane density of the Interferon-gamma receptor. Collectively, our findings reveal the importance of endomembrane trafficking in outfitting tumour cells with the ability to shape their immune microenvironment and respond to immunotherapy.

2024-06-27 | GSE253093 | GEO

Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [bulk RNA-seq]

2024-06-27 | GSE253092 | GEO

Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [scRNA-seq]

Project description:Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [scRNA-seq]

| PRJNA1064030 | ENA

Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy [bulk RNA-seq]

| PRJNA1064026 | ENA

Tumour-intrinsic endomembrane trafficking by ARF6 shapes an immunosuppressive microenvironment that drives melanomagenesis and response to checkpoint blockade therapy.

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

2024-06-27 | GSE253094 | GEO

Auxin induction in wild type and arf6 arf8 flowers

Project description:The aim of this study was to examine the roles of Auxin Response Factors (ARFs) in flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were treated with 10 uM indole-3-acetic acid for thirty minutes to identify genes that respond rapidly to auxin in an ARF6/ARF8-dependent manner. Keywords: auxin response; comparison of wild type and arf6 arf8 mutants

2005-06-30 | GSE2847 | GEO

Transcription profiling of Arabidopsis ARF6 and ARF8 mutants during flower development

Project description:The aim of this study was to examine the contribution of ARF6 and ARF8 to flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Flowers from wild-type, arf6/arf6 ARF8/arf8, and arf6 arf8 plants were separated into stage 1-10 flowers, stage 11+12 flowers, and stage 13-14 flowers to define the developmental stages at which ARF6 and ARF8 are required for gene expression.

2007-06-28 | E-GEOD-2848 | biostudies-arrayexpress

Arf6 regulation of glycolytic metabolism and effector functions in neutrophils

Project description:Arf6 is a small GTPase regulating many cellular processes including cytoskeletal remodeling, receptor endocytosis, and phagocytosis of pathogens. Arf6 knockdown in neutrophil (PMN)-like cells was reported to inhibit chemotactic peptide-mediated activation of phospholipase D, the oxidative burst, and 2 integrin-dependent adhesion. In mice, the migration of PMNs knock out for Arf6 to the site of inflammation was diminished and associated with reduced cell surface expression of 2 integrins. Conditional knockout mice lacking Arf6 in PMNs were used to assess the impact of Arf6 depletion on the functions and gene expression profile of PMNs isolated from the mouse air pouch injected with lipopolysaccharide (LPS). The expression of several genes was modulated in PMNs-Arf6 cKO with Lpar6 and Lacc-1 being the most up-regulated and down-regulated genes, respectively. Decreased expressed of Lacc-1 was validated at the protein level in PMN-Arf6 cKO, and silencing of Arf6 in THP-1 monocytic cells delayed LPS-mediated Lacc-1 expression. Here we report that fMLP or zymosan-induced glycolysis and oxygen consumption rate were decreased in air pouch PMNs but not in BM PMNs of Arf6 cKO mice when compared to control floxed cells. Reduced oxygen consumption correlated with decreased production of superoxide and ROS. Depletion of Arf6 in mouse PMNs also reduced phagocytosis and interfered apoptosis. The data suggest that Arf6 regulates energy metabolism, which may contribute to impaired phagocytosis, ROS production, and apoptosis in PMN-Arf6 cKO. This study provides new information on the functions and the inflammatory pathways influenced by Arf6 in PMNs.

2021-05-28 | GSE151436 | GEO

Transcription profiling of Arabidopsis ARF6 and ARF8 mutants treated with indoleacetic acid (IAA)

Project description:The aim of this study was to examine the roles of Auxin Response Factors (ARFs) in flower gene expression. Flowers from arf6 arf8 plants undergo a developmental arrest at approximately stage 12, just prior to flower opening. Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were treated with 10 uM indole-3-acetic acid for thirty minutes to identify genes that respond rapidly to auxin in an ARF6/ARF8-dependent manner. Experiment Overall Design: Wild-type, ARF6/arf6 arf8/arf8, and arf6 arf8 plants were sprayed with 10 mM indole-3-acetic acid in 1% methanol, 0.05% Tween-20. Thirty minutes after treatment, flowers (stage 1-14) were collected, frozen in liquid nitrogen, and used for RNA extraction.

2007-07-11 | E-GEOD-2847 | biostudies-arrayexpress

ARF6 bi-directionally regulates the dendritic spine formation depending on neuronal maturation and activity

Project description:Recent studies reported contradictory results regarding the role of ADP-ribosylation factor 6 (ARF6), a small GTPase known to regulate actin cytoskeleton, in dendritic spine development and maintenance. We readdress this question, and found that ARF6 either positively or negatively regulates dendritic spine formation depending on neuronal maturation and activity. ARF6 activation facilitates filopodia to spines transition, increasing the spine formation in developing neurons while it decreases spine density in matured neurons. Consistently, genome-wide microarray analysis revealed that Arf6 activation in developing and matured neurons leads to opposite expression patterns of a subset of genes that are involved in neuronal morphology.

2015-04-02 | GSE40937 | GEO

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