ARID1A gene status shapes cancer immune phenotype and affects cancer immunotherapy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA545311 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-05-06 | GSE131918 | GEO
Project description:Development of gene expression signatures for partial downreualtion of ARID1A protein. ARID1A was down-regulated by si-RNA in a breast cancer cell, MDA-MB-157. Subsequently, RNAs was extracted from control siRNA treated cells or partially ARID1A-down regulated cells. cDNAs were synthesized and cRNAs were labeled using low input quick Amp labeling kit (Agilent). Aftere washing and dry, scanned by Agilent Technologies Micorarrray Scanner and calculated using Agilent Feature 10.7.3.1. control siRNA treated MDA-MB-157 breast cancer cells (MOK) and siRNA-midiated ARID1A-downregulated MDA-MB157 breast cancer cells.
2015-09-03 | E-GEOD-72669 | biostudies-arrayexpress
Project description:Whether cancer driver mutation(s) directly drives cancer immune phenotype and immune tolerance remains a standing question. ARID1A is a core member of the polymorphic BAF chromatin remodeling complex. ARID1A mutations frequently occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A gene status on cancer immunity. We demonstrate that ARID1A mutations, limited expression, and deficiency impair interferon(IFN)-responsive gene chromatin accessibility and expression, resulting in anemic T cell tumor infiltration, weakened tumor immunity, and shortened host survival in many human cancer histologies as well as in murine cancer models, and are negatively associated with immunotherapy response. Mechanistically, ARID1A interacts with EZH2 via its carboxyl terminal and antagonizes EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN-responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.
2020-05-06 | GSE131916 | GEO
Project description:Whether cancer driver mutation(s) directly drives cancer immune phenotype and immune tolerance remains a standing question. ARID1A is a core member of the polymorphic BAF chromatin remodeling complex. ARID1A mutations frequently occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A gene status on cancer immunity. We demonstrate that ARID1A mutations, limited expression, and deficiency impair interferon(IFN)-responsive gene chromatin accessibility and expression, resulting in anemic T cell tumor infiltration, weakened tumor immunity, and shortened host survival in many human cancer histologies as well as in murine cancer models, and are negatively associated with immunotherapy response. Mechanistically, ARID1A interacts with EZH2 via its carboxyl terminal and antagonizes EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN-responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.
2020-05-06 | GSE131917 | GEO
Project description:Whether cancer driver mutation(s) directly drives cancer immune phenotype and immune tolerance remains a standing question. ARID1A is a core member of the polymorphic BAF chromatin remodeling complex. ARID1A mutations frequently occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A gene status on cancer immunity. We demonstrate that ARID1A mutations, limited expression, and deficiency impair interferon(IFN)-responsive gene chromatin accessibility and expression, resulting in anemic T cell tumor infiltration, weakened tumor immunity, and shortened host survival in many human cancer histologies as well as in murine cancer models, and are negatively associated with immunotherapy response. Mechanistically, ARID1A interacts with EZH2 via its carboxyl terminal and antagonizes EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN-responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.
2020-05-06 | GSE131915 | GEO
Project description:The study identifies genes that are regulated by the loss of the chromatin remodeller subunit ARID1A in colorectal cancer cell lines. This gene is frequently mutated in colorectal cancer.
2019-06-11 | E-MTAB-7791 | biostudies-arrayexpress
Project description:AT-rich interactive domain-containing protein 1A (ARID1A), a SWI/SNF chromatin remodeling complex subunit, is frequently mutated across various cancer entities. ARID1A contributes to DNA damage response pathways, and we previously reported that ARID1A loss is associated with mutational signatures linked to DNA repair defects. Here we show that ARID1A is promoting both DNA double-strand breaks (DSBs) repair pathways, non-homologous end-joining (NHEJ) and homologous recombination (HR). ARID1A is accumulated at DSBs after DNA damage and regulates the chromatin loop formation at DSB sites by interacting with the cohesin subunit RAD21 and CTCF insulator protein promoting their enrichment around the DSBs. Further analysis demonstrates that ARID1A’s involvement in DSB repair is accompanied by alterations of chromatin accessibility and distribution of activating histone marks at DSBs. ARID1A binds to and promotes the recruitment of the HDAC1 to control transcription repression at these DSBs. Altogether, ARID1A simultaneously regulates DSB repair and transcription silencing in transcriptionally active chromatin. ARID1A depletion resulted in defective DSB repair, which subsequently led to accumulation of micronuclei, activation of cGAS-STING pathway and an increased expression of immunomodulatory cytokines and chemokines upon IR treatment. Furthermore, low ARID1A expression in cancer patients receiving radiotherapy was associated with higher infiltration of several immune cells. The high mutation rate of ARID1A in various cancer types highlights its clinical relevance as a promising biomarker that correlates with the level of immune regulatory cytokines and can estimate the levels of tumor-infiltrating immune cells and response to combination of radio- and immunotherapy.
2024-06-22 | PXD047225 | Pride
Project description:To investigate that ARID1A regulates transcription of genes encoding components of the GSH synthesis pathway, a genome-wide expression analysis of a panel of ARID1A-proficient and ARID1A-deficient cancer cells was performed.
2019-01-28 | GSE122926 | GEO
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE197749 | GEO
Project description:Chronic inflammation and immunosuppressive microenvironment promote prostate cancer (PCa) metastasis and diminish the responses to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation induced IKKb activation to shape immunosuppressive tumor microenvironment (TME). Prostate-specific deletion of Arid1a cooperates with Pten loss to produce a metastasis-prone tumors. We identify that polymorphonuclear myeloid-derived suppressor cells (MDSCs) as the major infiltrating immune cell type to cause immune evasion, and neutralization of MDSCs restricts metastasis of Arid1a deficient tumors. Mechanistically, inflammation cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via b-TRCP. ARID1A downregulation in turn silences the enhancer of A20 deubiquitinase, a critical negative regulator of NF-kB signaling, and thereby unleashing CXCR2 ligands-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-kB or CXCR2 combined with ICB for advanced PCa. Together, our findings highlight a critical role of ARID1A in MDSCs recruitment and demonstrate IKKb/ARID1A/NF-kB feedback axis integrating inflammation and the immunosuppression to drive PCa metastasis.
2022-11-07 | GSE197687 | GEO