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GSE32373
Mus musculus
4 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Regulatory T (Treg) maintain the tumor microenvironment in an immunosuppressive state preventing effective anti-tumor immune response. A possible strategy to overcome Treg cell suppression focuses on OX40, a costimulatory molecule expressed constitutively by Treg cells while induced in activated effector T (Teff) cells. OX40 stimulation by the agonist mAb OX86 inhibits Treg cell suppression and boosts Teff cell activation. Here we uncover the mechanisms underlying the therapeutic activity of OX86 treatment dissecting its distinct effects on Treg and on effector memory T (Tem) cells, which are the most abundant CD4+ populations strongly expressing OX40 at the tumor site. In response to OX86, tumor-infiltrating Treg cells produced significantly less interleukin 10 (IL-10), possibly in relation to a decrease in the transcription factor IRF1. Tem cells responded to OX86 by upregulating surface CD40L expression, providing a licensing signal to dendritic cells (DCs). The CD40L/CD40 axis was required for Tem cell-mediated in vitro DC maturation and in vivo DC migration. Accordingly, OX86 treatment was no longer therapeutic in CD40 KO mice. In conclusion, following OX40 stimulation, blockade of Treg cell suppression and enhancement of the Tem cell adjuvant effect both concurred to free DCs from immunosuppression and to activate the immune response against the tumor.
Publication Title
Intratumor OX40 stimulation inhibits IRF1 expression and IL-10 production by Treg cells while enhancing CD40L expression by effector memory T cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery.
Publication Title
Functional education of invariant NKT cells by dendritic cell tuning of SHP-1.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Sample Metadata Fields
Age, Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Analysis of gene expression of prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated.The hypothesis tested in the present study was that mast cells inhibition or absence impacted prostate tumor development and histotype. Results demonstrate that prostate tumors arisen in TRAMP mice in which mast cells are pharmacologically stabilized or genetically ablated have a neuroendocrine signature.
Publication Title
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina mouseRef-8 v1.1 expression beadchip
Description
Analysis of gene expression of 2 novel prostate tumor cell lines isolated from TRAMP mice and compared to normal prostate. T1525 cell line is a well differentiated adenocarcinoma with epithelial features, whereas T23 cell line displays the molecular signature of epithelial-to-mesenchymal transition.
Publication Title
Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers.
Sample Metadata Fields
Age, Specimen part, Cell line
View Samples- Mus musculus
- 74 Downloadable Samples
NextSeq 500
Description
Macrophages, dendritic cells, conventional CD4+ T cells, CD8+ T cells, and regulatory T cells isolated from mouse colon cancer model MC38 tumors implanted subcutaneously to young (3 month) and aged (12 month) mice were sequenced using ImmGen's standard ultra-low input RNA-seq pipeline, in order to study age-dependent differences in intraltumoral immune cell functions and their impact on tumor control Overall design: Samples collected at the Center for Systems Biology at Mass General Hospital, shipped frozen to a central location, and sequenced using ImmGen's standard RNA-seq pipeline
Publication Title
Age-related tumor growth in mice is related to integrin α 4 in CD8+ T cells.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Anopheles gambiae
- 6 Downloadable Samples
- Illumina Genome Analyzer II, Illumina HiSeq 2000
Description
Anopheles gambiae antennal and palpal transcriptome expression profiles (male and female)
Publication Title
Transcriptome profiling of chemosensory appendages in the malaria vector Anopheles gambiae reveals tissue- and sex-specific signatures of odor coding.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Anopheles gambiae
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
RNAseq from male testes
Publication Title
Odorant receptor-mediated sperm activation in disease vector mosquitoes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study characterizes the inflammatory processes in left-sided colitis, pancolitis, and UC-associated dysplasia at the transcriptional level in colonics biopsies in order to identify potential biomarkers and transcripts of importance for the carcinogenic behaviour of chronic inflammation
Publication Title
Transcriptional analysis of left-sided colitis, pancolitis, and ulcerative colitis-associated dysplasia.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Background. T cells in the thymus undergo opposing positive and negative selection processes so that the only T cells entering circulation are those bearing a T cell receptor (TCR) with a low affinity for self. The mechanism differentiating negative from positive selection is poorly understood, despite the fact that inherited defects in negative selection underlie organ-specific autoimmune disease in AIRE-deficient people and the non obese diabetic (NOD) mouse strain. Results. Here we use homogeneous populations of T cells undergoing either positive or negative selection in vivo together with genome-wide transcription profiling on microarrays to identify the gene expression differences underlying negative selection to an Aire-dependent organ-specific antigen, including the upregulation of a genomic cluster in the cytogenetic band 2F. Analysis of defective negative selection in the autoimmune-prone NOD strain demonstrates a global impairment in the induction of the negative selection response gene set, but little difference in positive selection response genes. Combining expression differences with genetic linkage data we identify differentially expressed candidate genes including Bim, Bnip3, Smox, Pdrg1, Id1, Pdcd1, Ly6c, Pdia3, Trim30 and Trim12. Conclusions. The data provide a molecular map of the negative selection response in vivo, and by analysis of deviations from this pathway in the autoimmune susceptible NOD strain, suggest that susceptibility arises from small expression differences in genes acting at multiple points in the pathway between the TCR and cell death.
Publication Title
Impairment of organ-specific T cell negative selection by diabetes susceptibility genes: genomic analysis by mRNA profiling.
Sample Metadata Fields
No sample metadata fields
View Samples