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RNA profiling of PB-020 and anti-PD-1 antibody treated MC38 tumor tissue

ABSTRACT: RNA profiling of PB-020 and anti-PD-1 antibody treated MC38 tumor tissue

PROVIDER: PRJNA783079 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17023485.fastq.gz	Fastqsanger.gz
	SRR17023486.fastq.gz	Fastqsanger.gz
	SRR17023487.fastq.gz	Fastqsanger.gz
	SRR17023488.fastq.gz	Fastqsanger.gz
	SRR17023489.fastq.gz	Fastqsanger.gz

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RNA profiling of PB-020 and anti-PD-1 antibody treated MC38 tumor tissue

Project description:Immune surveillance escaping is essential for survival of original tumor. Considering PB-020’s good pharmacokinetic properties, combined effect of PB-020 and immunotherapy drugs is worth studying. As PB-020 can effectively suppress mouse colorectal cancer cell lines in cell culture, we tested the effect of combining PB-020 with the anti-PD-1 monoclonal antibody RMP1-14 on the growth of subcutaneously implanted MC38 cells to C57BL/6 mice as a syngeneic mouse model of colorectal cancer. To clarify the molecular mechanism underling this anti-cancer therapy, we executed RNA sequencing of tumor sample obtained from the experiment above.

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Project description:We treated mice bearing MC38 tumors with anti-PD-1 antibody (twice each week) or D18 (once one week). CD4+ T cells, CD8+ T cells and DCs were respectively isolated from tumors by FACS and RNA-seq performed. The goals of this study are to identify the activated cellular pathways in different subtype cells with the combination treatment. Samples were sequenced on an Illumina Hiseq 4000 instrument. The sequence reads were aligned to mouse mm10 reference genome using STAR (2.4.0) and then assembled and quantified by HTSeq (0.6.1) with Gencode M8 as annotation. DESeq2 was used for differential gene expression analysis among subgroups. Hierarchical clustering and principal component analysis were plotted applying FactoMineR and gplots libraries in R. log2 [FPKM] was calculated for each gene. We found that Granzyme, IFNγ, TNF were up-regulated and the related interferon induction pathway was activated in CD8+ T cells; the Th1 pathway and interferon signaling pathway were activated in CD4+ T cells; the expression of interferon-related and antigen-presenting machinery-related genes were increased in DCs by the combination treatment.

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