Expression data from spleen-derived and tumor-induced CD11b+ MDSC
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PROVIDER: PRJNA434517 | ENA |
REPOSITORIES: ENA
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Project description:CD11b+ myeloid-derived suppressor cells (MDSCs) have been shown to become activated at the tumor site and acquired a more suppressive phenotype compared to the splenic counterpart. This activated status promotes cancer progression by creating an immune suppressive niche around the tumor, by providing nourishment to the neoplastic cells, and by promoting metastases. To start understanding the differences between splenic and tumor infiltrating CD11b, genome-wide transcriptome analysis was performed. 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 or the tumor infiltrate of tumor-bearing mice.
2020-06-21 | GSE110772 | GEO
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.
2010-06-16 | E-GEOD-21927 | biostudies-arrayexpress
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). Immuno-regulatory activity of both tumor-induced and BM-derived MDSCs (by GM-CSF and IL-6 treatment) was entirely dependent on C/EBP transcription factor (TF), a key component of the emergency myelopoiesis triggered by stress and inflammation. We used miR expression analysis to identify miRs which could drive MDSC recruitment/generation/activity by modulating specific TFs and pathway. In particular, we identified a miR signature of 79 miR differentially expressed between not suppressive CD11b+ cells and CD11b+ isolated from tumor mass and spleen of tumor-bearing mice. Moreover on the same samples we profiled gene expression with Affymetrix microarrays to perform an integrated analysis of mirna and gene expression. Keywords: Expression profiling by array
2015-07-23 | GSE39807 | GEO
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
2020-10-23 | GSE116596 | GEO
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.
2010-06-03 | GSE21927 | GEO
Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray G-MDSC (CD11b+Ly6G+Ly6Clow) were purifed from splenocytes in EL4 lymphoma tumor bearing mice by positive selection of Ly6G using microbeads isolation. Neutrophils were purified from ascitic fluids induced after injection of milk protein, casein by negative selection of F4/80 and positive selection of Ly6G using microbeads isolation. Their RNA was extracted and gene expression was analyzed using Affymetrix microarray.
2011-03-10 | E-GEOD-24102 | biostudies-arrayexpress
Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray
2011-03-10 | GSE24102 | GEO
Project description:Myeloid derived Suppressor cells (MDSC) are heterogenous popluation of cells consists of two major subsets namely the monocytic Gr-1dull/int. and granulocytic (Gr-1high). These distinct two subsets use different mechanism to inhibit T cell response. In addition, how the function of these subsets is regulated is not known yet. The Gr-1dull/int. MDSC are suppressing T cells through IFNg dependent nitric oxide dependent manner. However, the exact suppressive mechanism of Gr-1high MDSC is not clear. Here we studied the role of a cytokine IFNg on the suppressive function of Gr-1high MDSC by comparing the gene expression of Gr-1high cells cultured alone versus those cultured with T cells which donot produce IFNgamma. CD11b+Gr-1high cells were purified from the splenocyte of CT-26 colon tumor bearing mice. The purified CD11b+Gr-1high MDSCs were cultured with IFNg-/- antigen specific T cells and re- sorted after 48h and RNA was extracted and gene expression was analyzed using topic-defined PIQORTM Immunology Microarrays.
2011-09-08 | E-GEOD-32000 | biostudies-arrayexpress
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:Myeloid-derived suppressor cells (MDSC) represent a heterogeneous population of immature myeloid cells that accumulate in blood, liver, spleen and tumors upon chronic inflammation and tumor development in patients and mice. Acute hepatitis is characterized by a fast infiltration of inflammatory cells in the liver and increased enzymatic activity at this organ that could lead into liver fibrosis and cirrhosis. We have studied the biology of hepatic MDSC in acute hepatitis. Unexpectedly, hepatic MDSC, which accumulate in the liver of mice bearing subcutaneous tumors, failed to suppress inflammatory responses upon Con A injection, but instead were responsible for exacerbating acute liver damage. Phenotypic, genetic and functional studies demonstrated rapid changes of hepatic MDSC from a suppressor phenotype into a pro-inflammatory subset as early as 3 hours after Con A injection. An increase in the expression of pro-inflammatory cytokines, costimulatory molecules such as CD80, CD86 and CD40 along with a loss of suppressor function was noticed in mice upon Con A treatment. These changes were CD40-dependent and not found in CD40-/- MDSC. Interestingly, CD40 ligation of human MDSC in vitro resulted in down-regulation of arginase I expression and suppressor function. Finally, blockade of ROS production in hepatic MDSC ameliorated hepatocyte damage suggesting that MDSC mediated toxicity was ROS dependent. We believe that these findings reflect how MDSC plasticity can be modulated to promote inflammation, opening a new path for therapies targeting innate suppressive cells in cancer patients. EL4 tumors were established in C57BL/6 mice, then mice were injected either with PBS (n=3) or 12.5mg/kg Con A (n=3). Three hours later mice were sacrificed, liver CD11b+Gr-1+ cells were sorted and samples were processed for gene expression analysis.
2015-09-01 | E-GEOD-50949 | biostudies-arrayexpress