Similar Datasets
Project description:We found that PMN-MDSCs level is elevated in the advanced ICCs tissues and is positively associated with the METTL1 and m7G tRNA modification levels. We further showed that impaired m7G tRNA modification impedes the PMN-MDSCs infiltration and inhibits ICC progression. Mechanistically, METTL1-mediated m7G tRNA modification selectively regulates the translation of human CXCL8 and mouse Cxcl5 transcripts, which facilitates the migration of PMN-MDSCs via binding to their cognate receptor CXCR2. Co-blockade of METTL1 and CXCR2 significantly enhances the efficacy of anti-PD-1 treatment in ICC. Taken together, our study reveals the cellular and molecular basis of crosstalk between ICC cells and MDSCs in shaping TIME and affecting ICIs efficacy, which enables reasonable design of new combined therapy targeting dysregulated mRNA translation and suppressive TIME.
2024-09-22 | GSE214631 | GEO
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.
2022-05-04 | ST002160 | MetabolomicsWorkbench
Project description:Myeloid-derived suppressor cells (MDSCs) are key players in immune evasion, tumor progression and metastasis. MDSCs accumulate under various pathological states, and fall into two functionally and phenotypically distinct subsets: polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. These subsets have been studied extensively in humans and mice, yet to date no study has identified MDSC subsets in dogs with spontaneous tumors. As dogs are an excellent model for human tumor development and progression, we set out to identify PMN-MDSCs and M-MDSCs in clinical canine oncology patients. We identified MDSCs as hypodense MHC class II-CD5-CD21-CD11b+ cells and show for the first time that they can also be subdivided into polymorphonuclear (CADO48A+CD14-) and monocytic (CADO48A-CD14+) subsets. The transcriptomic signatures of PMN-MDSCs and M-MDSCs are distinct from each other and from those of conventional polymorphonuclear (PMN) and monocytic cells, respectively. Notably, bioinformatic analyses reveal a statistically significant similarity between canine and previously published human MDSC gene expression patterns. As in humans, peripheral blood frequencies of canine PMN-MDSCs and M-MDSCs are significantly different in dogs with cancer compared to healthy control dogs (PMN-MDSCs: p < .001; M-MDSCs: p < .01). Furthermore, a comparison of our canine MDSC RNA-seq data with transcriptomic results previously published for human and murine MDSCs highlights five commonly upregulated genes in PMN-MDSCs in all species, suggesting that these genes are evolutionarily conserved and functionally important. Interestingly, one gene has previously been implicated in PMN-MDSC function (MMP8), but four genes (LTF, LCN2, CAMP, EBP41L3) are novel in the context of PMN-MDSCs. Our findings therefore demonstrate for the first time that dogs have two distinct populations of MDSCs, characterized by specific phenotypic and transcriptomic signatures that share key features of human MDSC subsets. Importantly, by leveraging the power of evolution, we have identified additional conserved genes in PMN-MDSCs of multiple species which may play a role in MDSC function. Our findings therefore validate the dog as a model for studying MDSCs in the context of cancer.
2019-03-27 | GSE119353 | GEO
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.
2022-05-13 | GSE192850 | GEO
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.
2012-03-29 | E-GEOD-35398 | biostudies-arrayexpress
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.
2018-02-13 | GSE93359 | GEO
Project description:Analysis of MDSC subsets from naive blood and RMA-S blood and RMA-S tumor, respectively. Tumor-infiltrating MO-MDSCs changed their expression pattern compared to blood and exhibited high levels of chemokines Total RNA obtained from PMN-MDSCs and MO-MDSCs from naive blood or from blood and tumor of RMA-S bearing mice
2012-10-17 | E-GEOD-41620 | biostudies-arrayexpress
Project description:To identify lncRNAs involved in regulating PMN-MDSCs, an Arraystar lncRNA microarray was performed to determine the lncRNA expression profile in PMN-MDSCs. Compared to those in CD11b+Ly6G+ cells under physiological conditions, the expression of abundant lncRNAs was significantly higher in PMN-MDSCs from the tumor microenvironment. In these lncRNAs, lncRNA AK036396, whose sequencing information has been identified in the UCSC database, was one of the most significantly upregulated lncRNAs and its expression was confirmed by quantitative real-time PCR (qRT-PCR). In addition, microarray data indicated that Fcnb expression, which can be used to identify immature granuloctyes and is closely associated with granulocyte maturation, was one of the highest potential target molecules of lncRNA AK036396 in PMN-MDSCs.
2020-02-17 | GSE145364 | GEO
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.
2023-06-26 | GSE199602 | GEO