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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scRNA_VDJ-seq]

ABSTRACT: Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scRNA_VDJ-seq]

PROVIDER: PRJNA1091881 | ENA |

REPOSITORIES: ENA

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [RNA-Seq]

Project description:T-cell exhaustion (Tex) phenotype has limited the efficacy of single-agent immune checkpoint blockade (ICB) in cancer immunotherapy, underscoring the need to target upstream pathways. Clinical trials have indicated that CXCR4 antagonists enhance anti-cancer activity. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood. By targeting CXCR4 using antagonists or transgenic mice (Cxcr4flox/flox LckCre), we effectively attenuated the Tex phenotype and enhanced the functional T-cell phenotype in vivo. Additionally, single-cell RNA/TCR-seq analyses demonstrated that CXCR4 inhibition promotes anti-PD-1 immunotherapy by reducing CD8+ Tex phenotype and enriching the abundance of TCR clonotypes in vivo. Mechanically, we found that CXCR4-blocking T cells mitigate Tex phenotype by regulating the JAK2-STAT3 pathway, reducing the interaction between p-STAT3 and TOX. Single-cell ATAC/RNA-seq validated that CXCR4 deficiency epigenetically orchestrates the transition from functional to exhausted phenotypes in CD8+ T cells. Altogether, we demonstrate a mechanism of targeting CXCR4 to orchestrate CD8+ Tex cells in cancers and provide a rationale for the combined CXCR4 antagonists and ICBs in clinical trials.

2025-01-28 | GSE255180 | GEO

Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [ChIP-Seq]

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scRNA_VDJ-seq]

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway

Project description:Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scATAC-seq; scRNA-seq]

2025-01-28 | GSE262444 | GEO

Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [ChIP-Seq]

Project description:Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [ChIP-Seq]

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [RNA-Seq]

Project description:Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [RNA-Seq]

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scATAC-seq scRNA-seq]

Project description:Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [scATAC-seq scRNA-seq]

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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway

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

2025-01-28 | GSE255182 | GEO

Oncogenic role of TOX in CTCL

Project description:TOX is a nuclear factor essential for the development of CD4+ T cells in the thymus. TOX is found to be aberrantly up-regulated in the skin biopsies and in the blood CD4+ T cells of cutaneous T cell lymphoma. The goal of this study is to identify potential transcriptional targets of TOX in CTCL by comparison between TOX shRNA transfected CTCL cells (Hut78 and HH) and control CTCL cells. Two color experiment. Lentivirus transduced control vector vs. TOX shRNA vectors on Hut78 and HH cell lines. Biological replicates: 3 control replicates, 3 shRNA tansduced replicates for each cell line.

2014-04-29 | E-GEOD-57122 | biostudies-arrayexpress

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