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:Therapies based on PD-1/PD-L1 blockade fail in most cancer patients. Here we evaluated the capacities of oleuropein to reprogram tumor-associated immunosuppressive myeloid cells to increase the potency of immunotherapies. Oleuropein caused major global reprogramming of monocytic and granulocytic myeloid-derived suppressor cells and tumor-associated macrophages towards immunostimulatory subsets. Differential quantitative proteomics uncovered activated and down-modulated pathways at high resolution for each subset which regulated major differentiation programs. Oleuropein significantly potentiated the capacities of myeloid cells to activate T-cells and enhanced antitumor properties of PD-1 blockade, either by systemic anti-PD-1 antibody administration, or locally by intratumor antibody delivery with a self-amplifying RNA vector based on Semliki Forest virus. Combination therapies decreased tumor infiltration by immunosuppressive myeloid cells and increased dendritic cell recruitment within draining lymph nodes, leading to systemic antitumor T-cell responses. Potent therapeutic activities were evident in lung cancer models resistant to immunotherapies and in colon cancer models.
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:Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer
Project description:Tumor-infiltrating monocytic myeloid-derived suppressor cells contribute to the development of an immunosuppressive tumor microenvironment in gastric cancer
Project description:Tumor-infiltrating Monocytic Myeloid-derived suppressor cells play a key role in forming immunosuppressive microenvironment in human gastric cancer
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.
