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Mus musculus
36 Downloadable Samples
Illumina HiSeq 2500
Description
Depletion of immunosuppressive tumor-associated macrophages (TAM) or reprogramming towards a pro-inflammatory activation state represent different strategies to therapeutically target this frequent myeloid population. Here we report that inhibition of colony-stimulating factor-1 receptor (CSF-1R) signaling sensitizes TAM to profound reprogramming in the presence of a CD40 agonist prior to their depletion. Despite the short-lived nature of macrophage hyperactivation, combined CSF-1R/CD40 stimulation of macrophages is sufficient to trigger a productive and durable T cell response in various mouse cancer models. The central role of macrophages in regulating T cell-dependent tumor rejections was substantiated by depletion experiments and transcriptomic analysis of ex vivo sorted TAM. Since CD40 expression on human TAM varies between different tumor types, co-expression of human CSF-1R and CD40 in colorectal adenocarcinoma and mesothelioma can serve as criteria to select these tumor types for clinical development Overall design: Female C57BL/6N mice (6-8 weeks in age, obtained from Charles River) were inoculated with 106 MC38 colorectal adenocarcinoma tumor cells subcutaneously. Tumor growth curves were monitored by caliper measurement and once tumor size reached 250 mm3 in average, groups were allocated for antibody treatment. Ten mice/group were treated with 30 mg/kg IgG1 isotype control antibody clone MOPC-21 (BioXCell), 4 mg/kg anti-CD40 rat IgG2a antibody clone FGK45 (BioXCell), 30mg/kg anti-CSF-1R antibody clone 2G2, 4 mg/kg rat IgG2a control clone 2A3 (BioXCell). For depletion experiments 4mg/kg mouse anti-CD4 antibody clone GK1.5 (Biolegend), 4mg/kg anti-NK1.1 antibody clone PK136 (BioXCell) and 4mg/kg anti-CD8a antibody clone 53-6.7 (BioXCell) were administered when tumor size reached 190mm3 in average. Antibodies were given every second day for four times. In between doses two and three of the depleting antibodies, animals were further treated with vehicle control (0,9% sodium saline), MOPC21, FGK45, 2G2 or combination of FGK45 and 2G2. The anti-CSF-1R antibody or respective IgG1 control antibody were administered weekly until tumors regressed completely or animals reached termination criteria, while the anti-CD40 antibody was only administered once at day 11 simultaneously with the anti-CSF-1R antibody. All antibodies were given intraperitoneally. All procedures were performed in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and European Union directives and guidelines.
Publication Title
Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE63862- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to understand the transcriptional effects of CD44s expression in a cell line that does not express CD44 in its native form we transfected CD44s into HEK cells and measured the transcriptional chances compared to native HEK cells
Publication Title
CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in Cancer Patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The effectiveness of new cancer therapies such as checkpoint blockade and adoptive cell transfer of activated anti-tumor T cells requires overcoming immunosuppressive tumor microenvironments. We found that the activation of tumor-infiltrating myeloid cells to produce local nitric oxide is a prerequisite for adoptively transferred CD8+ cytotoxic T cells to destroy tumors. These myeloid cells are phenotypically similar to Tip-DCs or nitric oxide- and TNF-producing dendritic cells. The nitric oxide-dependent killing was tempered by coincident arginase 1 expression, which competes with iNOS for arginine, the substrate for nitric oxide production. Depletion of immunosuppressive CSF-1R-dependent arginase 1+ myeloid cells enhanced nitric oxide-dependent tumor killing. Tumor killing via iNOS was independent of the microbiota but dependent on the CD40-CD40L pathway and, in part, lymphotoxin alpha. We extended our findings in mice to uncover a strong correlation between iNOS, CD40 and TNF expression and survival in colorectal cancer patients. Our results identify a network of anti-tumor targets to boost the efficacy of cancer immunotherapies.
Publication Title
T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We stratified colorectal tumor samples using a new unsupervised, iterative method based on non-negative matrix factorization (NMF). The resulting five subtypes exhibited activation of specific signaling pathways, and significant differences in microsatellite status and tumor location. We could also align three CRC cell lines panels to these subtypes.
Publication Title
Subtypes of primary colorectal tumors correlate with response to targeted treatment in colorectal cell lines.
Sample Metadata Fields
Sex, Race
View Samples- Anopheles gambiae
- 104 Downloadable Samples
- Affymetrix Plasmodium/Anopheles Genome Array (plasmodiumanopheles)
Description
Anopheles gambiae,the primary African malarial mosquito, exhibits numerous behaviors that are under diel and circadian control, including locomotor activity, swarming, mating, host seeking, eclosion, egg laying and sugar feeding. However, little has been performed to elucidate the molecular basis for these daily rhythms. To study how gene expression is globally regulated by diel and circadian mechanisms, we have undertaken a DNA microarray analysis ofA. gambiaehead and bodies under 12:12 light:dark cycle (LD) and constant dark (DD, free-running) conditions. Zeitgeber Time (ZT) with ZT12 defined as time of lights OFF under the light:dark cycle, and ZT0 defined as end of the dawn transition. Circadian Time (CT) with CT0 defined as subjective dawn, inferred from ZT0 of the previous light:dark cycle.
Publication Title
Genome-wide profiling of diel and circadian gene expression in the malaria vector Anopheles gambiae.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Nitrogen and light are two major regulators of plant metabolism and development. While genes involved in the control of each of these signals have begun to be identified, regulators that integrate gene responses to nitrogen and light signals have yet to be determined.
Publication Title
Modeling the global effect of the basic-leucine zipper transcription factor 1 (bZIP1) on nitrogen and light regulation in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development, function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has been primarily known as a transcriptional activator inducing prostate-specific gene expression. Through integrative analysis of genome-wide AR occupancy and androgen-regulated gene expression, here we report AR as a globally acting transcriptional repressor. This repression is mediated by androgen responsive elements (ARE) and dictated by Polycomb group protein EZH2 and repressive chromatin remodeling. In embryonic stem cells, AR-repressed genes are occupied by EZH2 and harbor bivalent H3K4me3 and H3K27me3 modifications that are characteristic of differentiation regulators, the silencing of which maintains the undifferentiated state. Concordantly, these genes are silenced in castration-resistant prostate cancer rendering a stem cell-like lack of differentiation and tumor progression. Collectively, our data reveal an unexpected role of AR as a transcriptional repressor inhibiting non-prostatic differentiation and, upon excessive signaling, resulting in cancerous de-differentiation. It provides an innovative mechanism for castration resistance and highlights novel therapeutic strategies to treat advanced prostate cancer.
Publication Title
Cooperation between Polycomb and androgen receptor during oncogenic transformation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hsa-mir-365-2 is one of the two precursors that give rise to miR-365. We discovered that miR-365 directly regulates a lung cancer and developmental gene termed thyroid transcription factor 1 (TTF-1 or NKX2-1).
Publication Title
MiR-365 regulates lung cancer and developmental gene thyroid transcription factor 1.
Sample Metadata Fields
Cell line
View Samples GSE69408- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Aging within the human hematopoietic system associates with increased incidence of anemia and myeloid neoplasms, decreased bone marrow (BM) cellularity and reduced adaptive immune responses. Similar phenotypes have been observed in mice and shown, at least in part, to involve hematopoietic stem cells (HSCs). However, evidence supporting such an association within human hematopoiesis is still sparse and prompted us to detail characteristics of human hematopoietic stem and progenitor cells throughout ontogeny.
Publication Title
Human and Murine Hematopoietic Stem Cell Aging Is Associated with Functional Impairments and Intrinsic Megakaryocytic/Erythroid Bias.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To identify transcriptional targets altered in the embryonic heart after exposure to TCE, and possible protective effects of folate, we used DNA microarray technology to profile gene expression in embryonic mouse hearts with maternal TCE exposure and dietary changes in maternal folate. Results: Exposure to low doses of TCE (10ppb) caused extensive alterations in transcripts encoding proteins involved in transport, ion channel, transcription, differentiation, cytoskeleton, cell cycle and apoptosis. Exogenous folate did not offset the effects of TCE exposure on normal gene expression and both high and low levels of folate produced additional significant changes in gene expression. Conclusions: A mechanism where TCE induces a folate deficiency does not explain altered gene expression patterns in the embryonic mouse heart. The data further suggest that use of folate supplementation, in the presence of this toxin, may be detrimental and non-protective of the developing embryo.
Publication Title
Gene expression profiling in the fetal cardiac tissue after folate and low-dose trichloroethylene exposure.
Sample Metadata Fields
Specimen part
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