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Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer

ABSTRACT: Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer

PROVIDER: PRJNA879091 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21523228_1.fastq.gz	Fastqsanger.gz
	SRR21523228_2.fastq.gz	Fastqsanger.gz
	SRR21523229_1.fastq.gz	Fastqsanger.gz
	SRR21523229_2.fastq.gz	Fastqsanger.gz
	SRR21523230_1.fastq.gz	Fastqsanger.gz

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Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer

Project description:Intratumoral T-cell dysfunction is a hallmark of pancreatic tumors, and efforts to improve dendritic cell (DC)-mediated T-cell activation may be critical in treating these immune therapy unresponsive tumors. Recent evidence indicates that mechanisms that induce dysfunction of type 1 conventional DCs (cDC1) in pancreatic adenocarcinomas (PDAC) are drivers of the lack of responsiveness to checkpoint immunotherapy. However, the impact of PDAC on systemic type 2 cDC2 development and function has not been well studied. Herein, we report the analysis of 3 cohorts, totaling 106 samples, of human blood and bone marrow (BM) from patients with PDAC for changes in cDCs. We found that circulating cDC2s and their progenitors were significantly decreased in the blood of patients with PDAC, and repressed numbers of cDC2s were associated with poor prognosis. Serum cytokine analyses identified IL6 as significantly elevated in patients with PDAC and negatively correlated with cDC numbers. In vitro, IL6 impaired the differentiation of cDC1s and cDC2s from BM progenitors. Single-cell RNA sequencing analysis of human cDC progenitors in the BM and blood of patients with PDAC showed an upregulation of the IL6/STAT3 pathway and a corresponding impairment of antigen processing and presentation. These results suggested that cDC2s were systemically suppressed by inflammatory cytokines, which was linked to impaired antitumor immunity.

2022-10-21 | GSE213096 | GEO

Systemic Alterations in Type-2 Conventional Dendritic Cells Lead to Impaired Tumor Immunity in Pancreatic Cancer.

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Short-term dietary changes lead to windows of mucosal and systemic immune depression

Project description:Short-term dietary changes lead to windows of mucosal and systemic immune depression

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Heterozygous mutations in SMARCA2 lead to impaired neurogenesis due to global retargeting of SMARCA4

Project description:Heterozygous mutations in SMARCA2 lead to impaired neurogenesis due to global retargeting of SMARCA4

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Germline ERCC6L2 mutations lead to impaired erythropoiesis and reshaping of the bone marrow niche

Project description:Germline ERCC6L2 mutations lead to impaired erythropoiesis and reshaping of the bone marrow niche

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Transcription profiling of Drosophila Roo lines grown on lead containing food to investigate lead toxicity

Project description:75 Diosophilia Roo lines, recominant inbred lines, were raised to adulthood either on conventional diet or diet supplemented with lead acetate. Whole flies were used for RNA extraction. RNA was run on Dros Genome 2 arrays. Each line also genotyped for 88 markers; Control food consisted of standard cornmeal, agar, sugar, yeast, and 250 microM NaAc (Ashburner 1989). Lead-contaminated food consisted of standard food plus 250 microM PbAc (lead exposure at this concentration has been shown to affect locomotion in adults (Hirsch et al. 2003)). Experiment Overall Design: 75 RI lines each line treated and untreated with lead acetate

2009-06-08 | E-GEOD-11695 | biostudies-arrayexpress

Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo.

Project description:Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo.

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Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo

Project description:Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo

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Genetical toxicogenomics of lead treatment

Project description:75 Diosophilia Roo lines, recominant inbred lines, were raised to adulthood either on conventional diet or diet supplemented with lead acetate. Whole flies were used for RNA extraction. RNA was run on Dros Genome 2 arrays. Each line also genotyped for 88 markers Control food consisted of standard cornmeal, agar, sugar, yeast, and 250 microM NaAc (Ashburner 1989). Lead-contaminated food consisted of standard food plus 250 microM PbAc (lead exposure at this concentration has been shown to affect locomotion in adults (Hirsch et al. 2003)). Keywords: genetical genomic

2009-06-01 | GSE11695 | GEO

Migratory CD11b+ conventional dendritic cells induce T follicular helper cell dependent antibody responses

Project description:T follicular helper (Tfh) cells are a subset of CD4+ T cells that promote antibody production during vaccination. Conventional dendritic cells (cDCs) efficiently prime Tfh cells; however, conclusions regarding the nature of the cDC responsible for instructing Tfh cell differentiation have differed between recent studies. We found that these discrepancies might exist, in part, due to the unusual sites used for immunization in murine models, which differentially bias which DC subsets access antigen. We used intranasal immunization as a physiologically relevant route of exposure that we show delivers antigen to all tissue DC subsets. Using a combination of mice in which the function of individual DC subsets is impaired and different formulations of antigen delivery, we determined that CD11b+ migratory type 2 conventional DCs (cDC2s) are necessary and sufficient for Tfh induction. DC-specific deletion of the guanine nucleotide exchange factor DOCK8 resulted in an isolated loss of CD11b+ cDC2 but not CD103+ cDC1 migration to lung-draining lymph nodes. Impaired cDC2 migration or development in DC-specific Dock8 or Irf4 knockout mice, respectively, led to reduced Tfh cell and antibody development, whereas loss of CD103+ cDC1s in Batf3-/- mice did not. Loss of cDC2-mediated Tfh responses was associated with impaired antibody-mediated protection from live influenza virus challenge. We show that migratory cDC2s uniquely carry antigen into the sub-anatomic regions of the lymph node where Tfh cell priming occurs, the T-B border. This work identifies the DC responsible for Tfh cell-dependent antibody responses, in particular when antigen dose is limiting or is encountered at a mucosal site, which could ultimately inform the formulation and delivery of vaccines.

2017-12-01 | GSE103956 | GEO

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