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Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness

ABSTRACT: Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness

PROVIDER: PRJNA986937 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25009842.fastq.gz	Fastqsanger.gz
	SRR25009843.fastq.gz	Fastqsanger.gz
	SRR25009844.fastq.gz	Fastqsanger.gz
	SRR25009845.fastq.gz	Fastqsanger.gz
	SRR25009846.fastq.gz	Fastqsanger.gz

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MULTIMODAL STIMULATION SCREENS REVEAL UNIQUE AND SHARED GENES LIMITING T-CELL FITNESS

Project description:T-cell dysfunction genes limit antitumor activity and may serve as therapeutic targets. It has not been systematically studied whether there are regulators that either uniquely or broadly contribute to T-cell fitness. We performed genome-scale CRISPR/Cas9 knockout screens in primary CD8 T-cells to uncover genes negatively impacting on fitness upon three modes of stimulation: (1) intense stimulation, triggering activation-induced cell death (AICD); (2) acute stimulation, triggering T-cell expansion; (3) chronic stimulation, causing dysfunction. Besides established regulators, we uncovered genes controlling T-cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increased translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T-cell clustering amplified T-cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induced functional T-cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T-cell antitumor activity.

2024-02-16 | PXD043545 | Pride

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Ctbp1]

Project description:Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Ctbp1]

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Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [IntenseAcuteChronic_screen]

Project description:Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [IntenseAcuteChronic_screen]

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Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Dap5]

Project description:Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Dap5]

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Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Icam1]

Project description:Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Icam1]

| PRJNA986938 | ENA

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [IntenseAcuteChronic_screen]

Project description:It has not been systematically studied whether T-cell fitness regulators uniquely or broadly contribute to specific traits limiting antitumor activity. We performed genome-scale CRISPR/Cas9 knockout screens in primary CD8 T-cells to uncover genes negatively impacting on their fitness upon three modes of stimulation: (1) intense stimulation, causing activation-induced cell death (AICD); (2) acute stimulation, triggering T-cell expansion; (3) chronic stimulation, resulting in dysfunction. Besides established regulators, we uncovered several genes controlling T-cell fitness either specifically or commonly under various stimulation modalities. Ablation of Dap5, ranking highly in all three screens, increased translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T-cell clustering amplified T-cell expansion and effector functions after both acute and intense stimulation. Finally, inactivation of Ctbp1 induced T-cell persistence exclusively upon chronic stimulation. Our results functionally annotate T-cell fitness regulators based on their unique or shared contribution to traits limiting T-cell antitumor activity.

2024-02-15 | GSE251758 | GEO

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Icam1]

2024-02-15 | GSE235710 | GEO

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Dap5]

2024-02-15 | GSE235709 | GEO

Multimodal stimulation screens reveal unique and shared regulators limiting T-cell fitness [Ctbp1]

2024-02-15 | GSE235707 | GEO

Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.

Project description:Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to T cell fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 T cells to uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced cell death (AICD); (2) acute, triggering expansion; (3) chronic, causing dysfunction. Besides established regulators, we uncover genes controlling T cell fitness either specifically or commonly upon differential stimulation. Dap5 ablation, ranking highly in all three screens, increases translation while enhancing tumor killing. Loss of Icam1-mediated homotypic T cell clustering amplifies cell expansion and effector functions after both acute and intense stimulation. Lastly, Ctbp1 inactivation induces functional T cell persistence exclusively upon chronic stimulation. Our results functionally annotate fitness regulators based on their unique or shared contribution to traits limiting T cell antitumor activity.

| S-EPMC11003465 | biostudies-literature

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