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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion

ABSTRACT: NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion

PROVIDER: PRJNA862096 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR20627677.fastq.gz	Fastqsanger.gz
	SRR20627678.fastq.gz	Fastqsanger.gz
	SRR20627679.fastq.gz	Fastqsanger.gz
	SRR20630279.fastq.gz	Fastqsanger.gz
	SRR20627680.fastq.gz	Fastqsanger.gz

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion [NFAT5 KO]

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion [ATAC]

Project description:Persistent exposure to antigen during chronic infection or cancer renders T cells dysfunctional. The molecular mechanisms regulating this state of exhaustion are thought to be common in infection and cancer, despite obvious differences in their microenvironments. We discovered that NFAT5, an NFAT family member lacking an AP-1 docking site, is highly expressed in exhausted T cells responding to chronic infection and tumors but is a central player selectively in tumor-induced exhaustion. While NFAT5 overexpression in CD8+ T cells reduced tumor control, NFAT5 deletion improved tumor control by promoting the accumulation of tumor-specific CD8 T cells that expressed less TOX and PD-1 and produced more cytokines specifically among precursor exhausted cells. Conversely, NFAT5 did not promote T cell exhaustion during chronic infection. While NFAT5 expression was induced by TCR triggering, its transcriptional activity was specific to the tumor microenvironment and required hyperosmolarity. NFAT5 thus promotes CD8 T cell exhaustion in a tumor-selective fashion.

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion (CUT&Tag)

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion

Project description:To decipher if NFAT5 controls CD8 T cell exhaustion during chronic infection on a molecular level, we performed scRNA sequencing on sorted P14 WT and NFAT5 KO CD8 from the spleen of a chronic LCMV-infected mouse.

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion [NFAT5 KO]

Project description:To decipher the molecular mechanism of NFAT5 KO CD8 T cells, we performed RNA sequencing on sorted P14 CD8 TILs seven days after CD8 T cell transfer.

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NFAT5 induction by the tumor microenvironment enforces CD8 T cell exhaustion [overexpression]

Project description:To decipher the molecular mechanism of NFAT5 or NFAT1 CA-RIT overexpressing CD8 T cells, we performed RNA sequencing on sorted P1A CD8 TILs seven days after CD8 T cell transfer.

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