Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA95959 | ENA |
REPOSITORIES: ENA
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Project description:Active suppression of tumor-specific T lymphocytes can limit the immune-surveillance and immunotherapy efficacy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+/IL-4Rα+, inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+/IL-4Rα+ cells produce IL-13 and IFN-γ and integrate the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits are active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors has detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumorinduced immune dysfunctions. Experiment Overall Design: Labeled cRNA extracted from a a total of 9 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 3 control samples represented 3 replicates of RNA extracted from Cd11b cells purified from the spleen of tumor-free mice. The 6 samples obtained from tumor-bearing mice represented 3 replicates each of RNA extracted from Cd11b cells purified from the spleen of tumor-bearing mice. Three out of six samples were incubated for 24 hours in complete medium.
2009-04-29 | E-GEOD-5455 | biostudies-arrayexpress
Project description:Single-cell transcriptome profiling using a 3' droplet-based platform (Chromium,10x Genomics) of CD11b+ cells isolated from the spleen of control and tumor-bearing mice, treated or not with IFN gene therapy.
2019-05-16 | E-MTAB-6487 | biostudies-arrayexpress
Project description:Transcriptional profiling of FACS-sorted and splenic control mouse cells, comparing splenic cells from FVBneuN vs Neu+ expressing FVBneuN mice with Gr1+ CD11b+ sorted tumor-infiltrating mononuclear or splenic myeloid-derived suppressor cells 4 groups or conditions. Biological replicates: 2 or 3 per condition. One replicate array per sample. manuscript: van Deventer, H, J Burgents, QP Wu, R Woodford, WJ Brickey, I Allen, E McElvania-Tekippe, J Serody, and J Ting. (2010) The inflammasome component Nlrp3 impairs antitumor vaccine by enhancing the accumulation of tumor-associated myeloid-derived suppressor cells. Cancer Research. variable: cell type: splenic cells from normal FVB-neuN mice, splenic cells from Neu+ tumor-bearing FVB-neuN mice, Gr1+ CD11b+ sorted cells from tumor, Gr1+ CD11b+ sorted cells from spleen repear: biological replicate: #1, #2, #3
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Project description:scRNAseq profiling of FACS-sorted Trem2 +/+ (CD45.2+) and Trem2 -/- (CD45.1+) myeloid enriched (DAPI-CD45+Ly6G- CD3e-CD11b+ and/or CD11c+) fractions purified from KP-GFP bearing lungs (21 days after tumor delivery intravenously) isolated from mixed bone marrow chimeric mice.
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Project description:Myeloid derived suppressor cells (MDSC) in the tumor microenvironment suppress T-cell mediated immune surveillance that clears tumor cells. As such, MDSC promote tumor growth. There are two subtypes of tumor MDSC, CD11b+Ly6ChiLy6G- monocytic MDSC (M-MDSC) , and CD11b+Ly6ClowLy6Ghigh granulocytic MDSC (G-MDSC). Cells with these markers also exist in the spleen of tumor bearing mice or in the spleen of mice with tissue-specific inflammation. Some have argued that the tumor MDSC is an activated version of the spleen MDSC, implying that they are similar to one another. Here we isolated the MDSC subtypes from the RM-1 tumors and from the spleen of mice with prostatic inflammation (n=4 per subtype per tissue, 16 total samples). We then analyzed RNA from these cells to determine how the transcript profile was altered by tissue location and MDSC subtype. Platform: Affymetrix Mouse Gene 1.0 ST v1 Genechip
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Project description:Global gene expression studies were performed to determine whether the granulocytic-like MDSC populations from G-CSF treated mice resembled those of tumor-bearing (TB) mice more so than those of the non-tumor-bearing control (i.e., WT) at a molecular level. Splenic CD11b+Gr-1high cell populations from WT, G-CSF-treated or 4T1-TB mice were purified in two independent experiments by flow cytometry (> 98% purity) and subjected to whole genome expression profiling using Illumina microarrays.
2011-12-07 | E-GEOD-32209 | biostudies-arrayexpress
Project description:Expression data from the spleen of tumor bearing mice
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Project description:scRNAseq profiling of FACS-sorted myeloid enriched (DAPI-CD45+Ly6G- CD3e-CD11b+ and/or CD11c+) and lymphoid enriched (DAPI-CD45+Ly6G- CD3e+) fractions purified from murine lungs bearing KP-GFP tumor lesions (28 days after tumor delivery intravenously) isolated from Trem2+/+ and Trem2-/- animals
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Project description:Tumor growth is associated with a profound alteration of myelopoiesis, leading to recruitment of immunosuppressive cells known as myeloid-derived suppressor cells (MDSCs). Analyzing the cytokines affecting myelo-monocytic differentiation produced by various experimental tumors, we found that GM-CSF, G-CSF, and IL-6 allowed a rapid generation of MDSCs from precursors present in mouse and human bone marrow (BM). BM-MDSCs induced by GM-CSF+IL-6 possessed the highest tolerogenic activity, as revealed by the ability to impair the priming of IFN- -producing CD8+ T cells upon in vivo adoptive transfer. Moreover, adoptive transfer of syngeneic, GM-CSF+IL-6-conditioned MDSCs to diabetic mice transplanted with allogeneic pancreatic islets resulted in long term acceptance of the allograft and correction of the diabetic status. Cytokines inducing MDSCs acted on a common molecular pathway. Immunoregulatory activity of both tumor-induced and BM-derived MDSCs was entirely dependent on C/EBP transcription factor, a key component of the emergency myelopoiesis triggered by stress and inflammation. Adoptive transfer of tumor antigen-specific CD8+ T lymphocytes resulted in therapy of established tumors only in mice lacking C/EBP in myeloid compartment. These data unveil another link between inflammation and cancer and identify a novel molecular target to control tumor-induced immune suppression. We used gene expression analysis to identify those factors, secreted by tumor-infiltrating MDSC, which could drive emathopoiesis. Moreover we compare gene expression profile of tumor-induced MDSC, obtained from either the spleen and the tumor infiltrate of tumor bearing mice, and in vitro bone marrow-derived MDSC. CD11b+ cells were immunomagnetically enriched from various murine tissue and experimental conditions, and cRNA samples were prepared accordingly to Expression Analysis: Technical Manual. 701021 Rev. 5. Santa Clara, CA, Affymetrix; 2004, and hybridized to the Affymetrix GeneChip MOE430 2.0 array which contains more than 45,000 probe sets, representing more than 34,000 genes. CD11b+ cells obtained from the spleen of healthy BALB/c and C57BL/6 mice were used as reference sample for tumor induced CD11b+ MDSC, enriched from either the spleen and the tumor infiltrate of tumor-bearing mice. Moreover CD11b+ cells enriched from fresh bone marrow were used as reference sample for in vitro bone marrow-differentiated MDSC, obtained with either GM-CSF+IL-6 and GM-CSF+G-CSF 4 days cytokine cocktail treatment.
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Project description:Naïve Treg cells were purified from the resting spleens of FoxP3-GFP knock-in mice made in the 129/SvJ strain. Ascites Treg cells were tumor-associated FoxP3-GFP+ cells sorted from the tumor ascites of 129/SvJ mice IP-injected with 1 x 10e6 RMAS cells 5 days earlier; Spleen-T Treg cells were purified from the spleens of the same tumor-bearing mice. Keywords: in vivo samples
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