Gene expression profiles of tumor-induced pTregs and anergic tumor-specific CD4+ T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE113624 | GEO | 2018/04/26
REPOSITORIES: GEO
Similar Datasets
Project description:Gene expression profiles of tumor-induced pTregs and anergic tumor-specific CD4+ T cells
| PRJNA453408 | ENA
Project description:compare gene expression profiles between normal and anergic T cells and identify upregulated genes in anergic T cells Experiment Overall Design: RNA from normal Th1 T cell clone and anergic Th1 T cell clone made anergic by plate-bound anti-CD3 antibody were isolated and amplified for microarray analysis
2008-06-14 | E-GEOD-5960 | biostudies-arrayexpress
Project description:Anergic T cells are unable to respond to antigen though their TCR is specific for it. Chronic infections and cancer can induce a dsyfunctional immune response which cannot clear the cause of disease. We asked in how far anergic T cells are similar to antigen-exhausted ones.
2020-12-18 | GSE143738 | GEO
Project description:The NR4A family of nuclear receptors are upregulated by acute and chronic antigen stimulation, and play redundant, tolerogenic roles in T and B cells. To bypass their obligate function in the Treg lineage, we generated competitive chimeras with Nr4a1-/-Nr4a3-/- (double knockout or DKO) bone marrow mixed with congenically marked WT bone marrow at a 1:5 ratio. As a result of a defect in Treg production by DKO cells, Treg in mixed chimeras are almost exclusively of WT origin. By contrast, we generate an approximately 1:1 DKO:WT ratio in the peripheral T cell compartment because DKO cells escape negative selection. After reconstitution, we observed pronounced accumulation of anergic DKO CD4 T cells, but a defect in functional tolerance resulting in autoantibody production. Based on these studies and published literature, we hypothesize that the NR4A family regulate TCR-induced transcripts in both naive and anergic CD4 T cells. To identify such targets, we sorted naive and anergic CD4 T cells of either WT or DKO genotype (CD45.1+ or CD45.1-) on the basis of CD73/FR4/CD44 expression from these chimeras directly into RLT buffer. In parallel, we stimulated sorted naive CD4 T cells of each genotype in vitro with plate-bound anti-CD3 and anti-CD28 stimulation for 3 hrs and then generated RLT lysates. We made biological triplicate samples of each condition (naive WT and DKO, naive stimulated WT and DKO, anergic WT and DKO) resulting in 6 different populations x 3 replicates = 18 samples. Samples were subjected to library prep and bulk RNA sequencing to identify DEG.
2021-06-24 | GSE178782 | GEO
Project description:Chronic HCV infection remains a global health concern due to its involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin’s lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HCV in BNHL development, although mechanistic insight is lacking. We performed RNA-sequencing on peripheral B cells from patients with HCV, BNHL, and HCV-associated BNHL to identify unique and shared transcriptional profiles associated with transformation. In patients with HCV-associated BNHL, we observed enrichment of an anergic gene signature and evidence of clonal expansion that was correlated with expression of epigenetic regulatory genes. Our data support a role for viral-mediated clonal expansion of anergic-like B cells in HCV-associated BNHL development, and suggest epigenetic dysregulation as a potential mechanism driving expansion. We propose epigenetic mechanisms may be involved in both HCV-associated lymphoma and regulation of B cell anergy, representing an attractive target for clinical interventions.
2022-10-22 | GSE215876 | GEO
Project description:Chromatin accessibility of bone marrow conventional T cells, pTregs, tTregs, BMAC-induced Tregs and in vitro-induced Tregs were compared Bone marrow (BM) harbors a large repertoire of regulatory T (Treg) cells, which are essential in hematopoiesis and peripheral tolerance. Treg cell accumulation in BM has been viewed as a consequence of preferential immigration of thymus-derived Treg cells. Here we report a novel subset of antigen presenting cells, which expresses the autoimmune regulator (Aire). These BM Aire-expressing cells resemble a subset of CD138+B220-TACI+Blimp-1+MHC-II+ plasma cells (pc-BMACs) and express a diverse repertoire of tissue-restricted self-antigens. pc-BMACs present self-antigens to na ve CD4+ T cells and can efficiently convert these into functionally competent CD25+Foxp3+ bona fide peripheral Treg cells (pTregs) capable of exerting immune suppression in vitro and in vivo. Aire expression may contribute to the tolerogenic function of pc-BMACs as it regulates the expression of genes involved in pTreg induction and function, including Icosl and retinoic acid synthesis-related genes, Aldh1a2 and Aldh1b1. Our data thus demonstrate an Aire-expressing plasma cell subset in the BM capable to promote peripheral tolerance by ectopically expressing tissue-restricted self-antigens and generating pTregs.
2022-08-26 | GSE136648 | GEO
Project description:Oncolytic viruses (OVs), known for their cancer-killing characteristics, overturn tumor-associated defects in antigen presentation through the MHC class I pathway and induce protective neo antitumor CD8 T cell responses. Nonetheless, whether OVs shape the tumor MHC-I ligandome remains unknown. Here, we investigated if an OV induces the presentation of novel MHC I-bound tumor antigens (termed tumor MHC-I ligands). Using comparative mass spectrometry (MS)-based MHC-I ligandomics, we determined differential tumor MHC-I ligand expression following treatment with oncolytic reovirus in a murine ovarian cancer model. In vitro we found that reovirus induces the presentation of tumor MHC-I ligands in cancer cells. Concurrent multiplexed quantitative proteomics revealed that the changes in tumor MHC-I ligand presentation were mostly independent of reovirus-induced alterations of their source proteins. In an in vivo model, tumor MHC-I ligands were induced by reovirus in tumors but also, more importantly, analysis of spleens (a source of antigen-presenting cells) showed exclusive induction of most MHC-I ligands occurred in tumor-bearing mice. Finally, IFNγ assays demonstrated immunogenicity of the reovirus-induced MHC-I ligands. OV-induced MHC-I responses may be exploited in combinatorial approaches to promote the efficacy of cancer immunotherapies.
2019-05-20 | PXD013066 | Pride
Project description:The elucidation of therapy-induced changes to the class I major histocompatibility complex (MHC-I)-bound tumor antigens is crucial for understanding immune-mediated tumor eradication and identifying potential targets for peptide vaccines to enhance the efficacy of immunotherapies. Here, we investigated how oncolytic reovirus therapy with and without immune checkpoint blockade (ICB) alters the tumor peptide-MHC repertoire. Using mass spectrometry analysis of immunoaffinity purified MHC peptides, we first showed that changes to the MHC immunopeptidome following reovirus treatment is cancer type-dependent, where a murine fibrosarcoma model displayed quantitative and qualitative variance in differentially expressed peptides (DEPs) as compared to those identified in a murine ovarian cancer model. We then determined that the combination therapy of reovirus and ICB in the fibrosarcoma model resulted in higher numbers of DEPs relative to either monotherapy alone. Most importantly, we identified reovirus and ICB-induced MHC peptides that are biologically active in stimulating interferon-gamma response in cognate CD8+ T cells, which likely contribute to cancer immunoediting. These findings highlight the importance of therapy-induced changes to the MHC immunopeptidome in shaping the underlying anti-tumor immune responses during reovirus and ICB combination therapy.
2021-12-06 | PXD024369 | Pride
Project description:Natural killer (NK) cell function is enhanced by interaction of inhibitory NK receptors with MHC class I molecules. NK cell function is critical during placentation, where these cells mediate adaptations to pregnancy in concert with other cells at the maternal/fetal interface. The aim of this experiment was to determine the downstream consequences on the uterine transcriptome that arise from lack of NK interaction with MHC class I molecules. This was done in mice lacking beta-2-microglobulin, thus not having correctly folded surface MHC class I. Biopsies were obtained from the mesometrial poles of the implantation chamber in gestation day (gd) 10.5 pregnant mice.
2018-11-01 | E-MTAB-4727 | biostudies-arrayexpress
Project description:Type II germ cell tumors (GCTs) are the most common neoplasia in young men of age 14-45 years. It is generally accepted that GCTs arise from a common precursor lesion, called germ cell neoplasia in situ (GCNIS), eventually developing into seminomas or non-seminomas, such as (embryonal carcinomas, ECs). The latter stem-cell like EC can further differentiate into teratomas (TE), yolk-sac tumors (YST), or choriocarcinomas (CC). Even though cisplatin-based chemotherapy is an efficacious standard of care during the management of GCT patients, the development of cisplatin resistance remains a major obstacle. As such, the surrounding tumor microenvironment and its secreted factors could endorse the development of drug resistance. These stromal cells, including immune cells (e.g. macrophages, T-lymphocytes), endothelial cells, and fibroblasts, can influence tumor cells by promoting proliferative and anti-apoptotic signaling pathways. Vice versa, microenvironmental cells can be influenced by tumor cells as well. For the identification of secreted proteins, cell lysates and supernatants from seven human germ cell tumor cell lines (seminoma: TCam-2; embryonal carcinoma (EC): 2102EP, NCCIT; choriocarcinoma (CC): JAR, JEG-3), yolk-sac tumor (YST): GCT72; 1411H) and five human cell types from the microenvironment (fibroblasts: MPAF, HVHF2; M2 macrophages: THP-1-M2; T-lymphocytes: JURKAT; endothelial cells: HUVEC) have been evaluated using liquid chromatography coupled with mass spectrometry (LC-MS).
2022-10-13 | PXD031329 | Pride