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Immunoediting of the cancer genome during tumor progression and activation of PD-1/PD-L1 axis in a mouse model of carcinoma

ABSTRACT: Immunoediting of the cancer genome during tumor progression and activation of PD-1/PD-L1 axis in a mouse model of carcinoma

PROVIDER: PRJNA359413 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5136260.fastq.gz	Fastqsanger.gz
	SRR5136270.fastq.gz	Fastqsanger.gz
	SRR5136261.fastq.gz	Fastqsanger.gz
	SRR5136271.fastq.gz	Fastqsanger.gz
	SRR5136262.fastq.gz	Fastqsanger.gz

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Immunoediting of the cancer genome during tumor progression and activation of PD-1/PD-L1 axis in a mouse model of carcinoma [SNP]

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Immunoediting of the cancer genome during tumor progression and activation of PD-1/PD-L1 axis in a mouse model of carcinoma [RNA-seq]

Project description:We designed a study to investigate immunoediting of an epithelial cancer genome using wildtype and immunodeficient mice, NGS, and analytical pipelines to process and analyze the data. We carried out experiments with wildtype and immunodeficient RAG1-/- mice with transplanted tumors and analyzed longitudinal samples with respect to the genomic landscape and the immunophenotypes of the tumors. Finally, we performed also experiments with anti-PD-L1 antibodies and show how the activation of the PD1-PD-L1 axis modulates immunoediting. MC38 cells were subcutaneously injected into wild-type C57Bl/6 and immunodeficient Rag1-/- mice. Samples were taken at predefined time points and subjected to detailed analysis, including FACS, exome sequencing, RNA sequencing and SNP arrays.

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Project description:Blocking the PD-1/PD-L1 immunosuppressive pathway has shown promise in the treatment of certain cancers including melanoma. This study investigates differences in the gene expression profiles of human melanomas that do or do not display the immunosuppressive protein PD-L1. Further understanding of genes expressed within the tumor microenvironment of PD-L1+ tumors may lead to improved rationally designed treatments. Gene expression profiling was performed on total RNA extracted by laser capture microdissection from 11 archived formalin-fixed paraffin-embedded (FFPE) melanoma specimens, 5 of which were PD-L1 positive and 6 PD-L1 negative. Details of the design, and the gene signatures found are given in the paper associated with this GEO Series: Janis M. Taube, Geoffrey D. Young, Tracee L. McMiller, Shuming Chen, January T. Salas, Theresa S. Pritchard, Haiying Xu, Alan K. Meeker, Jinshui Fan, Chris Cheadle, Alan E. Berger, Drew M. Pardoll, and Suzanne L. Topalian, Differential expression of immune-regulatory genes associated with PD-L1 display in melanoma: implications for PD-1 pathway blockade, Clin Cancer Res 2015, in press.

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