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RNA-seq analysis of gene expression regulated by LSD1 in CD8+ TILs

ABSTRACT: RNA-seq analysis of gene expression regulated by LSD1 in CD8+ TILs

PROVIDER: PRJNA613073 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11336213_1.fastq.gz	Fastqsanger.gz
	SRR11336213_2.fastq.gz	Fastqsanger.gz
	SRR11336214_1.fastq.gz	Fastqsanger.gz
	SRR11336214_2.fastq.gz	Fastqsanger.gz
	SRR11336215_1.fastq.gz	Fastqsanger.gz

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RNA-seq analysis of gene expression regulated by LSD1 in CD8+ TILs

Project description:T cell dysfunction is a hallmark of many cancers. Features of dysfunctional T cells and mechanisms leading to T cell dysfunction remain incompletely understood. Significant chromatin changes happen when T cells become dysfunctional, implicating a critical role of epigenetic regulators in such process. Here we study the role of LSD1 in regulating T cell function in cancer and perform a RNA-seq analysis of gene expression program controlled by LSD1.

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ChIP-seq analysis of gene expression regulated by LSD1 in CD8+ T cells

Project description:ChIP-seq assay was performed with GSK- or Vehicle-treated CD8+ T cells to interrogate the genome-wide distribution of LSD1, H3K4me1, H3K4me2, H3K4me3, H3K27ac, and Pol II, and their alterations in response to LSD1 inhibition.

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ChIP-seq analysis of gene expression regulated by LSD1 in CD8+ T cells

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RNA-seq analysis of gene expression regulated by LSD1 in CD8+ T cells

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Characterization of gene expression of tumor infiltrating T cells (TILs) in previously untreated patients with follicular lymphoma (FL) compared with those of tonsils

Project description:It has been shown that tumor infiltrating immune cells have a profound impact on the outcome of FL. To find mechanisms whereby TILs are altered gene expession analysis of highly pure TILs were performed. The study is composed of 4 groups, FL CD4 (n=12), FL CD8 (n=9), Tonsil CD4 (n=7) and Tonsil CD8 (n=7). All FL patients were treatment naive. Cells were flowsorted from cryopreserved single cell suspensions and purity of cells were at least 95%.

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Project description:CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.

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