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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [H1975 and HCC44]

ABSTRACT: SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [H1975 and HCC44]

PROVIDER: PRJNA1122777 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR29365031_1.fastq.gz	Fastqsanger.gz
	SRR29365031_2.fastq.gz	Fastqsanger.gz
	SRR29365032_1.fastq.gz	Fastqsanger.gz
	SRR29365032_2.fastq.gz	Fastqsanger.gz
	SRR29365033_1.fastq.gz	Fastqsanger.gz

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [H1975 and HCC44]

Project description:Genomic studies have identified frequent alterations in components of the SWI/SNF (SWItch/Sucrose Non- Fermenting) chromatin remodeling complex including SMARCA4 and ARID1A. Recent independent clinical studies have shown that SMARCA4 mutant lung cancer patients have very poor response to immunotherapy but the mechanism is unknown. Here we showed that SMARCA4 deficiency caused resistance to anti-PD1 immunotherapy and decreased CD4+ T cell and conventional class I dendritic cells (“cDC1s”) percentage in tumor microenvironment (TME) with mouse models. SMARCA4 loss in tumor cells prevented STING pathway sensing cytosolic DNA and cGAMP to reduce type I IFN and inflammatory cytokine gene expression. Importantly, SMARCA4 degradation induced a profound reprograming of the enhancer landscape with marked loss of chromatin accessibility at enhancers of genes involved in type I IFN and inflammatory cytokine, which is associated with nuclear factor NF-κB pathway. Our finding reveals that SMARCA4 loss can have a critical immune modulatory impact in cancer cell intrinsic fashion and suggest that manipulation of SMARCA4 in tumor cells can improve cancer immunotherapy.

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner II

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner II

Project description:SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner II

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [ChIP-seq3]

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [CUT&RUN]

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SMARCA4-mutant lung cancer disrupts anti-tumor immunity and immunotherapy response in a STING pathway-dependent manner [RNA-Seq]

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