Project description:p16 and p21 act as tumor suppressors through induction of cellular senescence. However, senescence-independent roles of these CDK inhibitors are not known. To identify the mechanism responsible for the failure of Mo-MDSCs (monocytic myeloid-derived suppressor cells) infiltration into tumor allografts in p16/p21-double knockout (DKO) mice, we searched for chemokine receptors that were highly expressed in Mo- but not PMN-MDSCs (polymorphonuclear myeloid-derived suppressor cells) and were downregulated in p16/p21-DKO as compared to WT Mo-MDSCs. Ccr2, Ccr5, and Cx3cr1 were identified by RNA-seq analysis.
Project description:Tumor derived factors can promote the differentiation of hematopoietic precursors into suppressive myeloid derived suppressor cells however, the molecular pathways that regulate this differentiation are not fully disclosed. In this study we identified a pathway by which tumor derived factors induce the expression of CCL3 and CCL4 from early HSPCs that autocrinally bind to CCR1 and CCR5 mediate the differentiation of BM cells into suppressive and protumoral cells. Inhibition of CCR1 and CCR5 is sufficient to prevent MDSC differentiation and restore the generation of myeloid cells with a tumoricidal function.
Project description:The aim of the study is to evaluate whether the preoperative level of myeloid-derived suppressor cells is associated with postoperative complications classified by Clavien-Dindo categories. Levels of all MDSC, polymorphonuclear MDSC (PMNMDSC), monocytic MDSC (MMDSC), early-stage MDSC (EMDSC) and monocytic to polymorphonuclear MDSC ratio (M/PMN MDCS) were established and compared in patients with postoperative complications, severe postoperative complications (>= IIIA according to Clavien-Dindo) and severe septic complications.
Project description:This is a ODE-based mathematical model featuring equations describing the dynamics of tumor cells, cytotoxic T cells, natural killer cells, and myeloid-derived suppressor cells (MDSCs) that together describe the tumor-induced immunosuppression caused by MDSCs.
Project description:Analysis of global gene expression in myeloid cells infiltrating tumors after irradiation. Cell death induces recruitment of myeloid cells into irradiated tumors thereby stimulating tumor recurrence. Results provide insights into molecular mechanisms regulating tumorigenic functions of myeloid cells in tumors re-growing after radiation therapy. Samples were collected at day 4 from irradiated tumors in WT, TLR9KO and Stat3KO (MxCre/Stat3flox). There were total 11 samples with 3-4 replicates of each sample type.
Project description:Analysis of global gene expression in myeloid cells infiltrating tumors after irradiation. Cell death induces recruitment of myeloid cells into irradiated tumors thereby stimulating tumor recurrence. Results provide insights into molecular mechanisms regulating tumorigenic functions of myeloid cells in tumors re-growing after radiation therapy.
Project description:Myeloid derived suppressor cells (MDSCs) were sorted from B16 tumor-bearing mice that were untreated or given lymphodepleting cyclophosphamide and fludarbine. We report that monocytic and polymorphonuclear MDSC subsets (M-MDSCs and PMN-MDSCs respectively) have a unique gene expression profile in comparison to MDSCs collected from untreated tumor-bearing animals.
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
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
Project description:Myeloid derived suppressor cells (MDSCs) were sorted from B16 tumor-bearing mice, WT and IL-6KO, that were untreated or given lymphodepleting cyclophosphamide and fludarbine. We report that monocytic and polymorphonuclear MDSC subsets (M-MDSCs and PMN-MDSCs respectively) have a unique gene expression profile in comparison to MDSCs collected from untreated tumor-bearing animals.
