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Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPRseq]

ABSTRACT: Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPRseq]

PROVIDER: PRJNA642292 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12102100.fastq.gz	Fastqsanger.gz
	SRR12102101.fastq.gz	Fastqsanger.gz
	SRR12102102.fastq.gz	Fastqsanger.gz
	SRR12102103.fastq.gz	Fastqsanger.gz
	SRR12102104.fastq.gz	Fastqsanger.gz

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Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing

Project description:Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing

| PRJNA630662 | ENA

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPRseq]

Project description:The genetic circuits that allow cancer cells to evade destruction by the host immune system remain poorly understood. To identify a phenotypically robust core set of genes and pathways that facilitate cancer cell-intrinsic evasion to cytotoxic T lymphocyte (CTL)-mediated killing, we performed genome-wide CRISPR screens across a panel of genetically diverse cancer models cultured in the presence of CTLs. We uncovered a core set of 182 genes whose individual perturbation leads to either cancer cell sensitivity or resistance to CTL toxicity. Systematic exploration of our dataset using genetic co-similarity reveals the hierarchical and coordinated nature by which genes and pathways act to orchestrate intrinsic CTL evasion, with discrete functional modules controlling the interferon response and tumor necrosis factor alpha (TNFa)-induced cytotoxicity emerging as dominant sub-phenotypes. Our data establish a central role for previously identified negative regulators of the Type II interferon response (e.g. Ptpn2, Socs1, Adar1) in mediating intrinsic CTL evasion and demonstrate a requirement for the lipid droplet related gene Fitm2 for maintaining cell fitness upon exposure to interferon gamma (IFNg). Additionally, we identify the autophagy pathway as a conserved mediator of cancer intrinsic CTL evasion, required to resist cytokine-mediated cytotoxicity caused by IFNg and TNFa. By mapping cytokine- and CTL-based genetic interactions, as well as in vivo CRISPR screens, we illuminate the pleiotropic nature by which autophagy acts to orchestrate intrinsic CTL evasion and highlight the importance of our observed effects within the tumor microenvironment. Collectively, our data expands our appreciation of the genetic circuits that contribute to cancer intrinsic immune evasion, highlighting the importance of leveraging systematic functional genomics approaches for furthering our understanding of this biology.

2020-07-31 | GSE153397 | GEO

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPR screen]

2020-07-31 | GSE149933 | GEO

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq II]

2020-07-31 | GSE149935 | GEO

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq I]

2020-07-31 | GSE149934 | GEO

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPR screen]

Project description:Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [CRISPR screen]

| PRJNA630664 | ENA

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq II]

Project description:Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq II]

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Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq I]

Project description:Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing [RNA-seq I]

| PRJNA630665 | ENA

Functional genomic landscape of cancer-intrinsic immune evasion to cytotoxic T lymphocyte killing

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

2020-07-31 | GSE149936 | GEO

Genome-wide CRISPR screen to identfy immune evasion genes in pancreatic cancer

Project description:Here we systematically dissected PDA intrinsic mechanisms of immune evasion by in vitro and in vivo CRISPR screening. Beyond the conserved set of genes regulating anti-cancer immunity we identified Rnf31 and Vps4b as essential factors required for escaping CD8+ T cell-killing. While the absence of Rnf31 induced sensitivity to T cell killing through TNF-mediated apoptosis in murine cancer cells and human PDA organoids, loss of Vps4b abrogated functional autophagy, resulting in accumulation of CD8+ T cell-derived granzyme B and subsequent tumor cell lysis.

2021-07-27 | GSE180834 | GEO

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