Project description:Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), also named pathologically activated neutrophil, is a critical component of tumor microenvironment (TME), playing crucial roles in tumor progression and therapy resistance. Here, we compared the transcriptome of PMN-MDSCs from B16 tumor bearing mice and the neutrophils from tumor free mice.
Project description:It is suggested that decidual polymorphonuclear myeloid-derived suppressor cell (PMN-MDSCs) are a group of activated suppressive neutrophils. Decidual microenvironment can facilitate circulating neutrophils with phenotypes and functions of PMN-MDSCs. The mechanism of PMN-MDSCs differentiation induced by decidual microenvironment has not been fully understood. Here we performed whole genome expression profile of 3 decidual PMN-MDSCs and autologous neutrophils from normal early pregnancy. Total RNA were extracted. The arrays were scanned by the Agilent Scanner G2505C. There were differences of gene expression pattern between decidual PMN-MDSCs and autologous neutrophils in early normal pregnancy.
Project description:Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), also named pathologically activated neutrophil, is a critical component of tumor microenvironment (TME), playing crucial roles in tumor progression and therapy resistance. CD300ld is specifically expressed in normal neutrophils and is upregulated in PMN-MDSCs upon tumor bearing. CD300ld knockout (KO) inhibits the development of multiple tumor types in a PMN-MDSC-dependent manner. Here, we compared the transcriptome of PMN-MDSCs from WT mice and CD300ld KO mice.
Project description:In prostate cancer patients following 3 months of white button mushroom consumption in freeze-dried tablet form, we observed the decline of circulating polymorphonuclear MDSCs (PMN-MDSCs), along with an increase of granzyme B positive CD8+ T cells and NK cells. Furthermore, single immune cell profiling of peripheral blood from WBM-treated patients revealed the transcriptional landscape of circulating immune cells. This methods showed a decrease in overall circulating PMN-MDSCs with suppression on the expression of STAT3/IRF1 and TGFβ signaling. Subclusters of PMN-MDSCs showed transcriptional profiles associated with "response to fungus", "neutrophil chemotaxis", "leukocyte aggregation", and "regulation of inflammatory response", which are associated with enhanced immune-modulated anti-tumor activity.
Project description:Development of Multiple Myeloma is associated with an accumulation of myeloid derived suppressor cells (MDSCs ) - cells that are morphologically and phenotypically similar to neutrophils (PMN-MDSC) and monocytes (M-MDSC), but are distinct in their functional and biochemical characteristics as well as in their ability to suppress immune responses. In our study, we found that both neutrophils and PMN-MDSCs equally promoted MM survival and decreased MM cell sensitivity to chemotherapy. Therefore, we used a microarray to elucidate the mechanism of the protective effect of neutrophils on myeloma cells.
Project description:Pathologically activated neutrophils (PMN), termed myeloid-derived suppressor cells (PMN-MDSCs), are major negative regulators of anti-tumor immunity. The mechanisms responsible for the pathological activation of neutrophils upon infiltration into tumors are not well defined, thus limiting the selective targeting of these cells. Tumor cells and immune cells engage in bi-directional manipulation of their respective metabolism, thereby altering cell function to facilitate tumor progression. Targeting the metabolism of responding immune cells can improve cancer treatment when combined with existing therapeutic strategies. Here, we investigated the role of metabolism in the immunoinhibitory actions of tumor PMN-MDSCs.
Project description:In prostate cancer patients following 3 months of white button mushroom consumption in freeze-dried tablet form, we observed the decline of circulating polymorphonuclear MDSCs (PMN-MDSCs), along with an increase of granzyme B positive CD8+ T cells and NK cells. Furthermore, single immune cell profiling of peripheral blood from WBM-treated patients revealed the transcriptional landscape of circulating immune cells. This methods showed a decrease in overall circulating PMN-MDSCs with suppression on the expression of STAT3/IRF1 and TGFβ signaling. Subclusters of PMN-MDSCs showed transcriptional profiles associated with "response to fungus", "neutrophil chemotaxis", "leukocyte aggregation", and "regulation of inflammatory response", which are associated with enhanced immune-modulated anti-tumor activity.
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:Decidual microenvironment can induce circulating neutrophils to acquire the phenotypes and functions of decidual polymorphonuclear myeloid-derived suppressor cell (PMN-MDSCs). The mechanism of PMN-MDSCs differentiation induced by decidual microenvironment has not been fully understood. Here we performed whole genome expression profile of neutrophils treated with decidual explant supernatant (DES) or not (n=3). Total RNA were extracted. Transcriptome libraries were generated with the Illumina TruseqTM RNA sample prep Kit, and sequencing was performed on the Illumina Novaseq 6000 platform. There were differences of gene expression after DES treatment.