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Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer

ABSTRACT: Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer

PROVIDER: PRJNA732400 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14631300_1.fastq.gz	Fastqsanger.gz
	SRR14631300_2.fastq.gz	Fastqsanger.gz
	SRR14633600_1.fastq.gz	Fastqsanger.gz
	SRR14633600_2.fastq.gz	Fastqsanger.gz
	SRR14631301_1.fastq.gz	Fastqsanger.gz

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Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [RNA-seq]

Project description:Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [RNA-seq]

| PRJNA732352 | ENA

Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [CUT&RUN]

Project description:Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [CUT&RUN]

| PRJNA732399 | ENA

Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [CUT&RUN]

Project description:Increases in terminally exhausted T cells in the tumor are associated with poor responses to immunotherapy, yet the mechanisms that promote progression to terminal exhaustion remain undefined. We profiled the chromatin landscape of subsets of tumor-infiltrating CD8+ T cells using CUT&RUN. CD8 T cells were sorted from the murine B16 melanoma tumor using PD1 and Tim3 expression to define four subsets: PD1lo, PD1mid, PD1hi, and PD1hiTim3+. Additional control samples include paired CD44+ cells from the tumor-draining lymph node of tumor bearing mice, and OT-I effector CD8 T cells isolated from Vaccinia-ova infection. We performed CUT&RUN for H3K4me3, H3K27me3, H3K27ac, and H3K9ac, as well as the transcription factors Tox and Batf.

2022-08-04 | GSE175437 | GEO

Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer [RNA-seq]

Project description:Increases in terminally exhausted T cells in the tumor are associated with poor responses to immunotherapy, yet the mechanisms that promote progression to terminal exhaustion remain undefined. To understand the effect of epigenetic changes in subsets of tumor-infiltrating CD8+ T cells, we performed RNA-seq to understand changes in gene expression. CD8 T cells were sorted from the murine B16 melanoma tumor using PD1 and Tim3 expression to define four subsets: PD1lo, PD1mid, PD1hi, and PD1hiTim3+. Additional control samples include paired CD44+ cells from the tumor-draining lymph node of tumor bearing mice, and OT-I effector CD8 T cells isolated from Vaccinia-ova infection. CD8 TIL PD1hi Tim3+ from B16 tumors treated with IgG control, anti-PD1 or anti-41BB agonist immunotherapies were also isolated for RNAseq.

2022-08-04 | GSE175408 | GEO

Altered costimulatory signaling and hypoxia support chromatin landscapes that limit the functional potential of exhausted T cells in cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-08-04 | GSE175443 | GEO

Single-cell RNA-seq of human breast tumor samples with exhausted and non-exhausted immune environments

Project description:Fresh human breast tumor tissue was dissociated into single cells and viably frozen. Patient samples were annotated as having an ""exhausted"" or ""non-exhausted"" immune environment based on CyTOF characterization of T cell phenotypes (Wagner et al, Cell 2019). 14 samples (7 exhausted, 7 non-exhausted) were selected for scRNA-seq (without prior cell type enrichment) with the goal to compare the two immune environment types and to comprehensively characterize exhaustion-associated features of the tumor microenvironment.

2023-08-25 | E-MTAB-10607 | biostudies-arrayexpress

Tumor microenvironmental signals reshape chromatin landscapes to limit the functional potential of exhausted T cells.

Project description: Not available

| S-EPMC9851604 | biostudies-literature

CD39 expression identifies terminally exhausted CD8+ T cells

Project description:Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion. CD8+ T cells from subjects with HCV infection were sorted and pelleted and re-suspended in TRIzol (Invitrogen). RNA extraction was performed using the RNAdvance Tissue Isolation kit (Agencourt). Concentrations of total RNA were determined with a Nanodrop spectrophotometer or Ribogreen RNA quantification kits (Molecular Probes/Invitrogen). RNA purity was determined by Bioanalyzer 2100 traces (Agilent Technologies). Total RNA was amplified with the WT-Ovation Pico RNA Amplification system (NuGEN) according to the manufacturer's instructions. After fragmentation and biotinylation, cDNA was hybridized to HG-U133A 2.0 microarrays (Affymetrix).

2015-09-08 | E-GEOD-72752 | biostudies-arrayexpress

Krüppel-like factor 4 regulates the cytolytic effector function of exhausted CD8 T-cells [ATAC-Seq]

Project description:Since exhausted CD8 T-cells are known to have a strong epigenetic imprint, which is a major obstacle for reinvigoration, we investigated whether the induced Klf4 expression could change the epigenetic status of the exhausted CD8 T-cells. For this, we performed ATAC-sequencing and compared chromatin landscapes between naïve, in vitro generated effector, exhausted (GFP-induced), and reinvigorated (KLF4-induced) CD8 T-cells.

2022-10-24 | GSE212805 | GEO

Human single cell RNA-sequencing reveals a targetable CD8+ exhausted T cell population that maintains murine low-grade glioma growth

Project description:Immune cell infiltration is a common feature of solid cancers, where T cells typically function as cytotoxic effectors to limit tumor growth, prompting therapies that activate this antineoplastic property (immune checkpoint inhibition; ICI). Unfortunately, ICI treatments have been largely ineffective for high-grade brain tumors (gliomas; HGGs). Leveraging several single-cell RNA sequencing datasets, we report greater CD8+ exhausted T cells in human pediatric low-grade gliomas (LGGs) relative to adult and pediatric HGGs. Using several preclinical mouse LGG models (Nf1-OPG mice), we showed that these PD1+/TIGIT+ CD8+ terminally exhausted T cells are restricted to the tumor tissue, where they express paracrine factors necessary for OPG growth. Importantly, ICI treatments with anti-PD1 and anti-TIGIT antibodies attenuate Nf1-OPG tumor proliferation through suppression of cytokine-mediated immune axis support, rather than by T cell-mediated cytotoxicity. Collectively, these findings establish a previously unrecognized function for CD8+ exhausted T cells as specialized regulators of LGG maintenance.

2024-10-23 | GSE244433 | GEO

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