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EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion

ABSTRACT: EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion

PROVIDER: PRJNA597045 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10748882.fastq.gz	Fastqsanger.gz
	SRR10748883.fastq.gz	Fastqsanger.gz
	SRR10748884.fastq.gz	Fastqsanger.gz
	SRR10748885.fastq.gz	Fastqsanger.gz
	SRR10748886.fastq.gz	Fastqsanger.gz

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EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion

Project description:Direct competition between tumor-infiltrating lymphocytes (TIL) and cancer cells for metabolic resources often renders T cells dysfunctional. Here, we report an epigenetic mechanism contributing to the development of metabolic exhaustion in TILs. T cells undergo a loss of the histone methyltransferase EZH2 (Enhancer of Zeste Homolog 2) during tumor infiltration. Using a multi-omics approach, we have defined a mechanism by which EZH2 inhibition leads to mitochondrial dysfunction and the resultant metabolic exhaustion. Reprogramming T cells to express a gain-of-function EZH2 mutant resulted in an enhanced ability of T cells to inhibit tumor growth. Our studies suggest that manipulation of EZH2 in T cells might represent a potential strategy to protect tumor-specific T cells during metabolic stress.

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EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion [RNA-seq]

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EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion [RNA-seq]

Project description:EZH2 protects tumor-infiltrating lymphocytes from metabolic-stress induced cell death and exhaustion [RNA-seq]

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