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Circulating PMN-MDSCs correlates with poor prognosis in metastatic hormone sensitive prostate cancer

ABSTRACT: Circulating PMN-MDSCs correlates with poor prognosis in metastatic hormone sensitive prostate cancer

PROVIDER: PRJNA853305 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19867250.fastq.gz	Fastqsanger.gz
	SRR19867251.fastq.gz	Fastqsanger.gz
	SRR19867252.fastq.gz	Fastqsanger.gz
	SRR19867253.fastq.gz	Fastqsanger.gz

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Circulating PMN-MDSCs correlates with poor prognosis in metastatic hormone sensitive prostate cancer

Project description:Myeloid-derived suppressor cells are recognized as a immunosuppressive cells in cancer but the characteritics in prostate cancer have not yet been known. We analyzed MDSCs and immune cells by single cell RNA sequence to clarify their variationos in prostate cancer.

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Effect of MS-275 and CXD101 on gene expression of M-MDSCs and PMN-MDSCs [RNA-Seq]

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Transcriptome comparison of PMN-MDSCs and and normal neutrophils

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.

2023-06-26 | GSE199601 | GEO

Spermidine restricts neonatal inflammation via metabolic shaping of PMN-MDSCs [CUT&Tag]

Project description:Newborns exhibit a heightened vulnerability to inflammatory disorders due to their underdeveloped immune system, yet the underlying mechanisms remain poorly understood. Here we report that plasma spermidine is correlated with the maturity of human newborns and reduced risk of inflammation. Administration of spermidine led to the remission of neonatal inflammation in mice. Mechanistic studies revealed that spermidine enhanced the generation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) via downstream eIF5A hypusination (eIF5A-Hyp). Genetic deficiency or pharmacological inhibition of deoxyhypusine synthase (DHPS), a key enzyme of eIF5A-Hyp, diminished the immunosuppressive activity of PMN-MDSCs, leading to aggravated neonatal inflammation. The eIF5A-Hyp pathway was found to enhance mitochondrial function via histone acetylation-mediated epigenetic transcription of immunosuppressive signatures in PMN-MDSCs. These findings demonstrated spermidine-eIF5A-Hyp metabolic axis as a master switch to restrict neonatal inflammation.

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Spermidine restricts neonatal inflammation via metabolic shaping of PMN-MDSCs [RNA-seq]

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White button mushroom intake modulates PMN-MDSCs, T, and NK cells’ function at the single cell level in prostate cancer patients

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.

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Transcriptome comparison of PMN-MDSCs and and normal neutrophils

Project description:Transcriptome comparison of PMN-MDSCs and and normal neutrophils

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Expression data from MDSCs at different time points during tumor progression

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 naÃ¯ve mice and Her-2/CT26 tumor-bearing mice. Total RNA was purified and gene expression was analyzed by the Affymetrix GeneChipÂ® Mouse Gene 1.0 ST Array.

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Uncovering common transcriptional features shared by mature PMN-MDSCs and tumor-associated neutrophils in humans

Project description:In this study, we performed single-cell transcriptomic profiling of mature PMN-MDSCs (mPMN-MDSCs) from non-small cell lung cancer (NSCLC) patients and identified a distinct cell cluster (NSCLC c6) exhibiting immunosuppressive and protumor features. Comparative analysis with publicly available single-cell RNA sequencing (scRNA-seq) datasets of tumor-associated neutrophils (TANs) revealed shared transcriptomic features between the identified NSCLC mPMN-MDSC and TAN clusters. These transcriptomic features included the expression of common genes, activation of the hypoxia signaling pathway, and metabolic reprogramming. Additionally, scRNA-seq analysis of mature immunosuppressive neutrophils from G-CSF-treated donors (GDs) – which are a reliable model of circulating mPMN-MDSCs - demonstrated similar dysregulation of hypoxia and metabolic pathways, further reinforcing the existence of transcriptomic similarities between circulating mPMN-MDSCs and TANs.

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