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Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [scRNA-Seq]

ABSTRACT: Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [scRNA-Seq]

PROVIDER: PRJNA549582 | ENA |

REPOSITORIES: ENA

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Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [scRNA-Seq]

Project description:CD8+ cytotoxic T cells play essential roles in anti-tumor immune responses. Here, we performed in vivo screens in CD8+ T cells and identified regulators of tumor infiltration and killing, which are directly relevant to cancer immunotherapy. Unlike in vitro screens, the in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8+ T cells against cancer in vivo. Immunological characterization in mouse and human CD8+ T cells revealed that DHX37 suppresses effector function, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating the NF-kB pathway. These data demonstrated the power of high-throughput in vivo genetic screens for immunotherapy target discovery, and uncovered DHX37 as a functional regulator of CD8+ T cells.

2019-08-22 | GSE132959 | GEO

Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [RNA-Seq]

2019-08-22 | GSE132926 | GEO

Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells

Project description:Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells

| PRJNA549581 | ENA

Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [RNA-Seq]

Project description:Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells [RNA-Seq]

| PRJNA549474 | ENA

Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-08-22 | GSE132960 | GEO

Project description:Systematic identification of immunotherapy targets using genome-scale in vivo CRISPR screens in CD8+ cytotoxic T cells

| PRJNA549266 | ENA

Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells.

Project description: Not available

| S-EPMC6719679 | biostudies-literature

Systematic Identification of Transcription Factors Driving Cell Fate Conversion using CRISPR Activation Screens

Project description:Systematic Identification of Transcription Factors Driving Cell Fate Conversion using CRISPR Activation Screens

| PRJNA487076 | ENA

Mast cell assisted In Vivo cancer Immunotherapy

Project description:Human Tumor Targeted Cytotoxic Mast Cells for Cancer Immunotherapy

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Impact of B16F0 exosomes on the transcriptome of CTLL2 cytotoxic T cells

Project description:While recent clinical studies demonstrate the promise of cancer immunotherapy, a barrier for broadening the clinical benefit is identifying how tumors locally suppress cytotoxic immunity. As an emerging mode of intercellular communication, exosomes secreted by malignant cells can deliver a complex payload of coding and non-coding RNA to cells within the tumor microenvironment. Here, we quantified the RNA payload within tumor-derived exosomes and the resulting dynamic transcriptomic response to cytotoxic T cells upon exosome delivery to better understand how tumor-derived exosomes can alter immune cell function. Exosomes derived from B16F0 melanoma cells were enriched for a subset of coding and non-coding RNAs that did not reflect the abundance in the parental cell. Upon exosome delivery, RNAseq revealed the dynamic changes in the transcriptome of CTLL2 cytotoxic T cells. In analyzing transiently co-expressed gene clusters, pathway enrichment suggested that the B16F0 exosomal payload altered mitochondrial respiration, which was confirmed independently, and upregulated genes associated with the Notch signaling pathway. Interestingly, exosomal miRNA appeared to have no systematic effect on downregulating target mRNA levels.

2018-03-13 | GSE103000 | GEO

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