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GSE29164
Mus musculus
24 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Myeloid-derived cells comprising the tumor stroma represent a heterogeneous population of cells critical to the structure, function and growth of established cancers. We have recently found that engineering tumor-specific CD8+ T cells to secrete IL-12 (IL-12TD) can lead to striking improvements in T-cell activity against established melanomas in murine models. Surprisingly, IL-12-dependent enhancement of CD8+ T-cell anti-tumor function did not occur through direct ligation of receptors on lymphocytes or NK cells. Instead, IL-12 sensitized host bone marrow-derived tumor-stromal cells, partly through interferon-gamma, to indirectly enhance the effects of adoptively-transferred T cells. Direct presentation of antigen by tumor was not necessary, but MHC class I expression on endogenous cells was essential for IL-12 mediated anti-tumor enhancements. Upon successful treatment with IL-12TD cells, we observed the selective elimination of tumor-infiltrating CD11b+ F4/80+ macrophages, CD11b+/ClassII+/CD11c+ dendritic cells and CD11b+/Ly6C+/Ly6G- but not CD11b+/Ly6C+/Ly6G+ myeloid-derived suppressor cells within regressing lesions. These results are consistent with a model whereby IL-12 triggers the maturation of myeloid-derived cells into competent antigen cross-presenting cells. Licensed recognition of these antigens by effector T cells may in turn trigger the collapse of the tumor stroma and aid in the regression of large vascularized lesions.
Publication Title
IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mouse CD8+ T cells affected by ID3 (Inhibitor of DNA binding 3) display patterns of gene expression suggesting enhanced persistance and survival. In this study, we identified genes differentially expressed between ID32a transduced and mock transduced, and ID32a knockout and wild type mouse CD8+ T cells. Most prominent functions of differentially expressed genes include DNA replication-associated repair, maintenance of chromosome stability and mitotic cell divison machinery. Overall, these data suggest that ID3 acts in favor of maintained survival in CD8+ mouse T cells.
Publication Title
Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects IFN-gamma on the differentiation and maturation of human peripheral blood monocyte-derived dendritic cells (moDC). Here, we report that following differentiation of human peripheral-blood monocytes into moDCs with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, interferon-gamma (IFN-gamma) induces moDC maturation and up-regulates the co-stimulatory markers CD80, CD86, CD95, and MHC Class I, enabling moDCs to effectively generate antigen-specific CD4+ and CD8+ T cell responses for multiple viral and tumor antigens. Interestingly, early exposure of monocytes to high concentrations of IFN-gamma promotes monocyte differentiation into macrophages, despite the presence of GM-CSF and IL-4. However, under low concentrations of IFN-gamma, monocytes continue to differentiate into dendritic cells possessing a unique gene-expression profile, resulting in impairments in subsequent maturation by IFN-gamma and an inability to generate effective antigen-specific CD4+ and CD8+ T cell responses compared to standard moDCs. Monocytes differentiated in the presence of low levels of IFN-gamma downregulate IFN-gamma receptor expression, impairing their response to an inflammatory rechallenge. These findings demonstrate the ability of IFN-gamma to impart differential programs on human moDCs which shape the antigen-specific T cell responses they induce. Timing and intensity of exposure to IFN-gamma can thus determine whether moDCs are tolerogenic or immunostimulating.
Publication Title
Timing and intensity of exposure to interferon-γ critically determines the function of monocyte-derived dendritic cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of nave or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from nave or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of nave cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their nave or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy.
Publication Title
Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Serial comparison between Th1 and Th17 tumor-specific cells cultured in vitro and ex vivo after transferred into sublethaly irradiated B6.PL mice. Th17-derived cells acquire Th1-like properties in vivo but maintain a distinct molecular profile.
Publication Title
Th17 cells are long lived and retain a stem cell-like molecular signature.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Comparison of gene expression changes of FACS sorted splenic CD11b+CD8a- and CD11b-CD8a+ cDC subsets reconstituted in vivo following total body irradiation in combination with exogenous retinoic acid or vehicle control.
Publication Title
Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
Long-term survival and antitumor immunity of adoptively transferred CD8+ T cells is dependent on their metabolic fitness, but approaches to isolate therapeutic T cells based on metabolic features are not well established. Here we utilized a lipophilic cationic dye tetramethylrhodamine methyl ester (TMRM) to identify and isolate metabolically robust T cells based on their mitochondrial membrane potential (??m). Comprehensive metabolomic and gene expression profiling demonstrated global features of improved metabolic fitness in low-??m-sorted CD8+ T cells. Transfer of these low-??m T cells was associated with superior long-term in vivo persistence and an enhanced capacity to eradicate established tumors compared with high-??m cells. Use of ??m-based sorting to enrich for cells with superior metabolic features was observed in CD8+, CD4+ T cell subsets, and long-term hematopoietic stem cells. This metabolism-based approach to cell selection may be broadly applicable to therapies involving the transfer of HSC or lymphocytes for the treatment of viral-associated illnesses and cancer. Overall design: mRNA-Sequencing of gene expression profiles in mouse CD8 cells (TMRM high and TMRM low).
Publication Title
Mitochondrial Membrane Potential Identifies Cells with Enhanced Stemness for Cellular Therapy.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Adoptive cell immunotherapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can result in complete regression of advanced melanoma in some patients, but the efficacy of this potentially curative therapy is limited by poor persistence of TIL after adoptive-transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in viral-specific murine models, but whether this approach may enhance features of memory (e.g. long-term persistence) in TIL which are characteristically exhausted and senescent is not established. Here we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments antitumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy for melanoma. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of anti-tumor T cells and improve the efficacy of cellbased immunotherapy for metastatic cancer.
Publication Title
Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Sus scrofa
- 206 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
In this study, we used correlation analysis of the expression profiles and carcass traits to produce a list of functional candidate genes under the assumption that genes with strong correlation between their expression values and drip belong to pathways or networks relevant for the control of the trait.
Publication Title
Elucidating molecular networks that either affect or respond to plasma cortisol concentration in target tissues of liver and muscle.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 29 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The inverted teat defect is an inherited disorder characterised by the failure of teats to protrude from the udder surface. The number and identity of relevant genes are unknown.
Publication Title
Microarray analysis reveals genes and functional networks relevant to the predisposition to inverted teats in pigs.
Sample Metadata Fields
Specimen part
View Samples