Expression data of human Tregs treated with TNFR2 agonist antibody
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ABSTRACT:
PROVIDER: PRJNA767809 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16148482.fastq.gz | Fastqsanger.gz | |||
| SRR16148483.fastq.gz | Fastqsanger.gz | |||
| SRR16148484.fastq.gz | Fastqsanger.gz | |||
| SRR16148485.fastq.gz | Fastqsanger.gz | |||
| SRR16148486.fastq.gz | Fastqsanger.gz |
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Project description:Tumor necrosis factor receptor 2 (TNFR2), a membrane-bound tumor necrosis factor receptor expressed by regulatory T cells (Tregs), participates in Treg proliferation. Although a specific TNFR2 pathway has been reported, the signaling mechanism has not been completely elucidated. This study sought to clarify TNFR2 signaling in human Tregs using amplicon sequencing and single-cell RNA-sequencing to assess Tregs treated with a TNFR2 agonist antibody. Pathway enrichment analysis based on differentially expressed genes highlighted tumor necrosis factor α signaling via nuclear factor-kappa B, interleukin-2 signal transducer and activator of transcription 5 signaling, interferon-γ response, and cell proliferation-related pathways in Tregs after TNFR2 activation. TNFR2-high Treg-focused analysis found that these pathways were fully activated in cancer Tregs, showing high TNFR2 expression. Collectively, these findings suggest that TNFR2 orchestrates multiple pathways in cancer Tregs, which could help cancer cells escape immune surveillance, making TNFR2 signaling a potential anticancer therapy target.
2022-01-10 | GSE185145 | GEO
Project description:Tumor necrosis factor receptor 2 (TNFR2), a membrane-bound tumor necrosis factor receptor expressed by regulatory T cells (Tregs), participates in Treg proliferation. Although a specific TNFR2 pathway has been reported, the signaling mechanism has not been completely elucidated. This study sought to clarify TNFR2 signaling in human Tregs using amplicon sequencing and single-cell RNA-sequencing to assess Tregs treated with a TNFR2 agonist antibody. Pathway enrichment analysis based on differentially expressed genes highlighted tumor necrosis factor α signaling via nuclear factor-kappa B, interleukin-2 signal transducer and activator of transcription 5 signaling, interferon-γ response, and cell proliferation-related pathways in Tregs after TNFR2 activation. TNFR2-high Treg-focused analysis found that these pathways were fully activated in cancer Tregs, showing high TNFR2 expression. Collectively, these findings suggest that TNFR2 orchestrates multiple pathways in cancer Tregs, which could help cancer cells escape immune surveillance, making TNFR2 signaling a potential anticancer therapy target.
2022-01-10 | GSE185144 | GEO
Project description:Single-cell RNA-seq data of human Tregs treated with TNFR2 agonist antibody
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Project description:This study aimed to explore the characteristics and role of TNFR2+ Tregs in the microenvironment and progression of gastric cancer by single-cell RNA sequencing.We obtained Tregs from tumor tissues and peripheral blood of three GC patients.Through single-cell RNA sequencing, we found tumor-infiltrating Tregs express high levels of TNFR2. The TNF-a/TNFR2 signaling pathway is activated, accompanied by upregulation of costimulatory molecules. Compared to blood Tregs, tumor-infiltrating Tregs exhibit activated and effector states. In addition to expressing costimulatory molecules such as TNFR2, 4-1BB, OX40 and GITR, tumor-infiltrating Tregs are also characterized by high expression of immune checkpoints such as CTLA-4 and TIGIT and chemokines such as CCR6.This study revealed a high infiltration level of TNFR2+ Tregs with the characteristics of activated and effector Tregs in the tumor microenvironment. Our study provides a new theoretical basis for TNFR2+ Tregs as a therapeutic target in gastric cancer.
2021-04-16 | GSE172131 | GEO
Project description:Expression data of iPS microglia treated with TREM2 agonist antibody
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing TNFα receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in PDAC patients. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing anti-tumoral responses. In orthotopic and immunocompetent mouse models of PDAC, we described the immune environment of PDAC after immune cell sorting and single-cell analysis. By flow cytometry and single cell RNAseq analysis, we identified two Treg populations in orthotopic mouse models: resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8+ T cells. However, anti-TNFR2 treatment alone had limited efficacy in activating CD8+ T cells and only slightly reduced the tumor growth.
2025-10-28 | GSE280808 | GEO
Project description:TNF is a pleiotropic cytokine that exerts immunomodulatory functions mostly mediated by its interaction with the receptor TNFR2, highly expressed by regulatory T cells. However, Tregs can also produce TNF, and the existence of an autocrine TNF-TNFR2 loop has been proposed. Here, we describe that, indeed, both human and mouse Tregs can produce TNF in physiological conditions, in several mouse organs, and in mouse models of chronic inflammation and cancer. However, TNF production and TNFR2 expression are mutually exclusive in Tregs: indeed, TNFR2+ and TNFR2- Treg subsets are respectively poor and strong TNF producers. In TNFR2+ cells, TNF is both transcriptionally and post-transcriptionally controlled, through the repressing activity of microRNA-146a. The two subsets of TNFR2+ and TNFR2- Tregs partially maintain their different ability to produce TNF, when separately stimulated ex vivo. However, when cocultured, the TNFR2+ cells greatly outnumber the TNFR2- counterpart, and induce in TNFR2- cells the upregulation of Foxp3 and TNFR2, an event that is associated with the transfer of cytoplasmic material from TNFR2+ to TNFR2- cells. Functionally, TNFR2+ Tregs are endowed with superior suppressive activity, in association with a better survival in vitro. This phenotype could be attributed to an improved resistance to oxidative stress, as revealed by gene expression analysis and intracellular ROS staining. Overall, our data indicate that Tregs exist in two states, respectively committed to TNF production or TNF sensing through TNFR2, which cooperate in promoting the suppressive function of the whole Treg pool.
2025-09-23 | GSE291595 | GEO
Project description:PURPOSE: The goal of this study was to determine the gene expression networks regulated by tumor necrosis factor receptor 2 (TNFR2, or Tnfrsf1b) and to evaluate their potential bearing on immune cell subsets and inflammatory bowel disease (IBD). METHODS: mRNA-seq was performed on isolated distal colons from TNFR2-knockout and wildtype mice. Differentially expressed transcripts were compared to human ulcerative colitis microarray datasets on Gene Expression Omnibus and to mouse immunological expression datasets at the Immunological Genome Project. RESULTS: We identified 252 mouse transcripts whose expressions were significantly altered by the loss of TNFR2. The majority of these transcripts (228 of 252, ~90%) were downregulated in TNFR2-/- colons. TNFR2-regulated genes were able to positively discriminate between ulcerative colitis patients and healthy individuals with ~80% accuracy. Many TNFR2-regulated genes were also highly expressed in CD8+ T cells. CONCLUSIONS: Downregulation of TNFR2 is associated with a gene expression profile that is prominent in IBD and supportive of the role of CD8+ T cells in IBD pathogenesis. MANUSCRIPT ABSTRACT: Increased tumor necrosis factor (TNF) production has been associated with inflammatory bowel disease (IBD), and anti-TNF therapy is a common therapeutic for this patient population. However, the role of TNF or its receptors (TNFR1 and TNFR2) in the immunopathogenesis of inflammatory bowel disease (IBD) remains unclear. Here we report that TNFR2 is protective in spontaneous (IL-10 knockout) and chemically (azoxymethane/dextran sodium sulfate)-induced mouse models of colitis and colitis-associated cancer. Mechanistically, TNFR2-deficiency in hematopoietic cells significantly increased incidence and severity of colitis and colitis-associated cancer characterized by a selective expansion of CD8+ T cells. We identified TNFR2-regulated genes in the colon that were specific for CD8+ T cells, interacted with multiple IBD risk genes, and are important regulators of CD8+ T cell biology. TNFR2 regulated CD8+ T-cell-specific genes that act as genetic susceptibility modifiers for IBD to mitigate the development of a pro-colitogenic milieu. Antibody-mediated depletion of CD8+ T cells prevented colonic inflammation and significantly reduced pathology in IL10-/-/TNFR2-/- deficient mice. Furthermore, adoptive transfer of TNFR2-/- naïve CD8+ T cells resulted in more severe disease than with wildtype naïve CD8+ T cells. Our findings provide insight into the disease modifier role of TNFR2 in the immunopathogenesis of IBD through the modulation of CD8+ T cell responses and support future investigation of this therapeutic target, especially in the subset of IBD patients with CD8+ T-cell dysfunction. Total RNA from distal colons of 8 week-old male wildtype C57Bl/6 and TNFR2-/- mice (n=3 each) was isolated using the PureLink RNA kit (Ambion, Life Technologies). RNA samples were submitted to the Genomic Services Lab at the HudsonAlpha Institute for Biotechnology (Huntsville, AL) for multiplex library preparation, mRNA enrichment, and sequencing. Sequencing was performed to an average depth of 50M paired-end 50bp reads per sample (HiSeq, Illumina, San Diego, CA). Data files containing raw reads were aligned to the mouse genome using Tophat2/Bowtie2. Alignments were assembled into transcript representations with Cufflinks, and statistical tests for differential expression were performed with Cuffdiff 2. An adjusted P value < 0.05 (q<0.05) from the Cuffdiff 2 output was used as the cutoff for statistical significance.
2015-08-11 | E-GEOD-65408 | biostudies-arrayexpress
Project description:The adenosine 2A receptor (A2AR) is expressed on regulatory T cells (Tregs), but the functional significance is currently unknown. We compared the gene expression between wild-type (WT) and A2AR knockout (KO) Tregs and between WT Tregs treated with vehicle or a selective A2AR agonist. FACS-sorted GFP positive Tregs from WT or A2AR KO FoxP3GFP mouse spleen and lymph nodes were incubated 18 hr with vehicle (DMSO), a separate set of WT Tregs were incubated with the selective A2AR agonist ATL1222 10 nM (Dogwood Pharmaceuticals, Inc.) for 18 hr prior to RNA isolation.
2012-05-31 | E-GEOD-34006 | biostudies-arrayexpress
Project description:We performed single-cell transcriptome and antibody repertoire sequencing of bone marrow and splenic B cells from mice of different age following protein (TNFR2) immunizations
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