Project description:Several mechanisms have been implicated in MDSC-mediated suppression of immune responses. To better understand the mechanism(s)/pathway(s) MDSCs utilize to suppress immune responses, we performed a transcriptome profiling of CD11b+CD11c+ (good suppressors) and CD11b+CD11c- (poor suppressors) MDSCs. Comparison of the respective transcriptomes allowed us to identify target genes associated with immunosuppression.
Project description:Myeloid derived suppressor cells (MDSCs) markedly expand and participate in the suppression of immune responses in inflammation and tumor microenvironment. It was confirmed that MDSCs could be generated in vitro from bone marrow cells (BMCs) after 4 days GM-CSF only or GM-CSF plus IL-6 treatment. To identify the regulation of MDSCs in tumor microenvironment, we analyzed the gene expression from tumor cell ID8 supernant-induced MDSCs compared to BMCs.
Project description:Myeloid-derived suppressor cells (MDSCs) as a population of myeloid cells enriched in cancer patients with immunosuppressive function. Further studies have determined that MDSCs are comprised of two groups: polymorphonuclear-MDSCs (G-MDSCs) and monocytic-MDSCs (M-MDSCs). We used a microbeads kit (Miltenyi) to isolate G-MDSCs and M-MDSCs with markers Ly6c2-Ly6g+CD11b+ and Ly6c2+Ly6g-CD11b+, respectively. And then using bulk RNA-seq to anlysis the enrichment gene expression in G-or M-MDSC which from wild type, APCmin mutant adenoma and immune deffiency mice.
Project description:We sorted the MDSCs from the bone marrows of B16-F10 tumor-bearing mice and the naive mice. In addition, we cultured MDSCs in vitro to determine the effect of DOX (5µM).
Project description:Myeloid-derived suppressor cells (MDSCs) comprise a hetergenous immune cell population that expands within the inflamed microenvironment of the stomach during pre-cancerous and cancerous lesion development in mouse. MDSCs are heterogeneous and this study aims to understand their diverse functions.
Project description:Myeloid-derived suppressor cells (MDSCs) are increased by tumor-derived factors and suppress anti-tumor immunity. MDSCs obtained at a late time point after tumor injection had stronger suppressive activity than MDSCs obtained at an early time point, as measured by T cell proliferation assays. To find factors in MDSCs that change during tumor growth, we analyzed gene expression profiles from MDSCs at different time points after tumor injection. We found that immune response-related genes were down-regulated, but pro-tumor function-related genes were up-regulated in both Mo-MDSCs and PMN-MDSCs at the late time point. Among differentially expressed genes, FK506 binding protein 51 (FKBP51), which is a member of the immunophilin protein family and plays a role in immunoregulation, was increased in the Mo- and PMN-MDSCs isolated from the late time points. Experiments using siRNA and a chemical inhibitor of FKBP51 revealed that FKBP51 contributes to the regulation of the suppressive function of MDSCs by increasing iNOS, ARG1, and ROS levels and enhancing NF-kappaB activity. Collectively, our data suggest that FKBP51 is a novel molecule that can be targeted to regulate the immunosuppressive function of MDSCs. To identify the factors that licensed MDSCs to be more suppressive as tumors grow, we analyzed gene expression profiles in the two subsets of MDSCs at different time points (3wks, 6wks) during tumor progression. CD11b+Ly-6C(high)Ly-6G(low) Mo-MDSCs and CD11b+Ly-6C(low)Ly-6G(high) PMN-MDSCs were sorted from pooled spleens of naïve mice and Her-2/CT26 tumor-bearing mice. Total RNA was purified and gene expression was analyzed by the Affymetrix GeneChip® Mouse Gene 1.0 ST Array.
Project description:Bone marrow-derived MDSCs were generated from bone marrow of naive WT or Rel-/- mice. After red blood cell lysis, BM cells were cultured in complete RPMI medium containing GM-CSF (100 ng/mL) and IL-6 (100 ng/mL) for 7 days. RNAs were collected afterwards for RNA-Seq.
Project description:Murine MDSCs isolated from the spleens of Lewis lung carcinoma mice were treated with or without WGP, and then miRNA array was used to analyze the differentailly expressed miRNAs. Murine MDSCs were isolated from the spleens of Lewis lung carcinoma tumor-bearing mice, and the sorted MDSCs were stimulated with or without 100 µg/ml WGP for 24 h. Then, the total RNA was extracted to perform miRNA array to analyze the differentially expressed miRNAs in MDSCs treated with or without WGP