This SuperSeries is composed of the SubSeries listed below.
Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.
Treatment
View SamplesTo define the gene profile altered by EZH2 and H3K27me3 in response to IFNg, we performed several microarrays in primary ovarian cancer cells transfected with shEZH2 or treated with GSK126. We found that 155 and 124 genes were altered by shEZH2 and GSK126 treatment, respectively, and 20 genes were increased or decreased by both shEZH2 and GSK126 treatment.
Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.
Treatment
View SamplesTo define the gene profile altered by EZH2 and H3K27me3 in response to IFNg, we performed several microarrays in primary ovarian cancer cells transfected with shEZH2 or treated with GSK126. We found that 155 and 124 genes were altered by shEZH2 and GSK126 treatment, respectively, and 20 genes were increased or decreased by both shEZH2 and GSK126 treatment.
Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy.
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View SamplesCD8+ T cells activated by cancer immunotherapy execute tumor clearance mainly by inducing cell death through perforin-granzyme- and Fas/Fas ligand-pathways. Ferroptosis is a form of cell death that differs from apoptosis and results from iron-dependent lipid peroxide accumulation. Although it was mechanistically illuminated in vitro, emerging evidence has shown that ferroptosis may be implicated in a variety of pathological scenarios. However, the involvement of ferroptosis in T cell immunity and cancer immunotherapy is unknown. Here, we find that immunotherapy-activated CD8+ T cells enhance ferroptosis-specific lipid peroxidation in tumor cells, and in turn, increased ferroptosis contributes to the anti-tumor efficacy of immunotherapy. Mechanistically, IFNg released from CD8+ T cells downregulates expression of SLC3A2 and SLC7A11, two subunits of glutamate-cystine antiporter system xc-, restrains tumor cell cystine uptake, and as a consequence, promotes tumor cell lipid peroxidation and ferroptosis. In preclinical models, depletion of cyst(e)ine by cyst(e)inase in combination with checkpoint blockade synergistically enhances T cell-mediated anti-tumor immunity and induces tumor cell ferroptosis. Thus, T cell-promoted tumor ferroptosis is a novel anti-tumor mechanism. Targeting tumor ferroptosis pathway constitutes a therapeutic approach in combination with checkpoint blockade. Overall design: Human HT-1080 mRNA profiles treated by IFNg for 8 hours was determined by RNA-Seq.
CD8<sup>+</sup> T cells regulate tumour ferroptosis during cancer immunotherapy.
Specimen part, Cell line, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesIdentify IL-2 mediated genes in Kit225 cells.
Genome wide mapping reveals PDE4B as an IL-2 induced STAT5 target gene in activated human PBMCs and lymphoid cancer cells.
Specimen part, Cell line
View SamplesThese data show that Paupar, a CNS expressed long non-coding RNA (lncRNA), directly and functionally associates with KAP1, an essential epigenetic regulatory protein. Transcriptome profiling of N2A cells identified 1,913 differentially expressed genes whose expression significantly changed (at a 5% false discovery rate [FDR]) greater than 1.4-fold (log2 fold change 0.5) upon KAP1 depletion. Examination of the intersection of KAP1 and Paupar transcriptional targets showed that Paupar and KAP1 control expression of a shared set of target genes that are enriched for regulators of neuronal function and cell cycle in N2A cells. Furthermore, CHART-seq and ChIP-seq derived Paupar-KAP1 genome-wide co-occupancy maps revealed a 4-fold enrichment of overlap between Paupar and KAP1 bound sequences on chromatin. This study also indicates that Paupar promotes KAP1 chromatin occupancy and H3K9me3 deposition at a subset of distal targets, through formation of a ribonucleoprotein complex containing Paupar, KAP1 and the PAX6 transcription factor. These observations provide important conceptual insights into the trans-acting modes of lncRNA-mediated epigenetic regulation and the mechanisms of KAP1 genomic recruitment.
The long non-coding RNA <i>Paupar</i> promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The long non-coding RNA <i>Paupar</i> promotes KAP1-dependent chromatin changes and regulates olfactory bulb neurogenesis.
Cell line
View SamplesDifferentiating human dendritic cells were stimulated for 12 hours with RXR agonists (LG268, 9CRA, R- and S-9CDHRA) or agonists for RXR partners including GW3965 (LXR/ panagonist), RSG (PPAR agonist), and GW1516 (PPAR agonist) and AM580 (RARa agonist). The gene expression changes were detected globally by Affymetrix Human Genome U133 Plus 2.0 Arrays.
9-cis-13,14-Dihydroretinoic Acid Is an Endogenous Retinoid Acting as RXR Ligand in Mice.
Specimen part, Subject
View SamplesRationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease.
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Specimen part, Disease
View Samples