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Next Generation Sequencing of tumor tissue (4T1 cell) of BALB/c

ABSTRACT: Next Generation Sequencing of tumor tissue (4T1 cell) of BALB/c

PROVIDER: PRJNA776639 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16646925.fastq.gz	Fastqsanger.gz
	SRR16646926.fastq.gz	Fastqsanger.gz
	SRR16646927.fastq.gz	Fastqsanger.gz
	SRR16646928.fastq.gz	Fastqsanger.gz
	SRR16646929.fastq.gz	Fastqsanger.gz

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TCR repertoire analysis by Next-generation sequencing of mouse CD8+ T cells in spleen or tumor

Project description:We have reported that intra-tumoral treatment with 1V270, a phospholipid-conjugated TLR7 agonist,induces local expansion an systemic dispersion of oligoclonal tumor-specific T cells by TCR repertoire analysis using next generation RNAseq methodology. Here, we examined whether systemic 1V270 therapy also induced oligoclonal expansion of tumor-specific T cells. Two groups of BALB/c mice (n=4/group) were i.p. treated with 1V270,a phospholipid-conjugated TLR7 agonist. One cohort of mice was i.v. injected with 4T1-GLF cells (2×104) on day 0. Another cohort did not receive i.v. tumor injection (no tumor-exposed mice). 4T1 cells were orthotopically inoculated on day 21. To examine clonal specificity of tumor-specific T cells, CD8+ cells were isolated from the spleens and the tumor infiltrating lymphocytes of secondarily challenged tumors after initial 1V270 therapy. The TCR repertoires were assessed by next generation RNA sequencing of both TCRαand TCR β genes.

2018-07-31 | E-MTAB-6566 | biostudies-arrayexpress

Next Generation Sequencing of tumor tissue (4T1 cell) of BALB/c

Project description:Immune checkpoint blockade (ICB), particularly programmed death 1 (PD-1) and its ligand (PD-L1), has shown considerable clinical benefits in patients with various cancers. Many studies show that PD-L1 expression may be biomarkers to help select responders for anti-PD-1 treatment. Therefore, it is necessary to elucidate the molecular mechanisms that control PD-L1 expression. As a potential chemosensitizer and anticancer drug, copper combined with disulfiram (DSF) kills tumor cells by regulating multiple signaling pathways and transcription factors in vitro and in vivo. Here, we showed that DSF increased PD-L1 expression in triple negative breast cancer (TNBC) cells. Through TCGA data analysis, we found that DNMT1 and IRF7 were highly expressed and the hypermethylation states in the IRF7 gene body promoter region in TNBC vs normal breast tissue (NBT). Then, we demonstrated that DSF affected PD-L1 expression via DNMT1-mediated IRF7 hypomethylation in two TNBC cell lines. In vivo experiments, DSF significantly enhanced the response to PD-1 antibody (Ab) in the triple-negative 4T1 BC mouse model. By analyzing the results of the tumor tissue sequencing, the DSF joint anti-PD-1 Ab could be a significant activation of anti-tumor immunity. And the inactive state of immune associated pathways was found to be reversed, such as Th1 and Th2 cell differentiation, antigen processing and presentation, natural killer cell-mediated cytotoxicity and T cell receptor signal transduction. In conclusion, we found that DSF could up-regulate PD-L1 in TNBC cells and elucidated its mechanism. Our findings revealed that the combination of DSF and anti-PD-1 Ab could activate the tumor immune microenvironment (TIME) to show much better antitumor efficacy than monotherapy.

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Gene expression profile at single cell level of immune cells from STING-NP treated 4T1 BALB/c tumors

Project description:scRNA-seq was performed on immune cells isolated from 4T1 BALB/c tumors to investigate their response to various treatments.

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Expression analysis of the effect of overexpression of Cebpb shRNA in mouse 4T1 mammary tumor cells

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Next generation sequencing analysis of epididymal adipose tissue (II)

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