Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [DNA-edit]

ABSTRACT: Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [DNA-edit]

PROVIDER: PRJNA934483 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23440557_1.fastq.gz	Fastqsanger.gz
	SRR23440557_2.fastq.gz	Fastqsanger.gz
	SRR23440558_1.fastq.gz	Fastqsanger.gz
	SRR23440558_2.fastq.gz	Fastqsanger.gz
	SRR23440559_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 48

Similar Datasets

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function

Project description:Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function

| PRJNA934314 | ENA

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [RNA-seq]

Project description:Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [RNA-seq]

| PRJNA934482 | ENA

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [DNA-edit]

Project description:Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we seek to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism, whereby cancer cells suppress T cell function by generating a metabolically unfavorable tumor microenvironment (TME). Specifically, we use an in silico screen to identify ADA and PDK1 as metabolic regulators, in which gene overexpression (OE) enhances the cytolysis of CD19-specific CD8 CAR-T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampens such effect. Additionally, ADA-OE in CAR-T cells improves cancer cytolysis under high concentrations of adenosine, the ADA substrate and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics in these CAR-Ts reveal alterations of global gene expression and metabolic signatures in both ADA- and PDK1- engineered CAR-T cells. Functional and immunological analyses demonstrate that ADA-OE increases proliferation and decreases exhaustion in α-CD19 and α-HER2 CAR-T cells. We then show ADA-OE improves tumor infiltration and clearance by α-HER2 CD4 and CD8 CAR-T with an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR-T cells, and reveal potential targets for improving CAR-T based cell therapy.

2023-05-18 | GSE225185 | GEO

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function [RNA-seq]

2023-05-18 | GSE225184 | GEO

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function

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

2023-05-18 | GSE225186 | GEO

Immunogenetic metabolomics revealed key enzymes that modulate CAR-T metabolism and function.

Project description:Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we seek to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism, whereby cancer cells suppress T cell function by generating a metabolically unfavorable tumor microenvironment (TME). Specifically, we use an in silico screen to identify ADA and PDK1 as metabolic regulators, in which gene overexpression (OE) enhances the cytolysis of CD19-specific CD8 CAR-T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampens such effect. ADA -OE in CAR-T cells improves cancer cytolysis under high concentrations of adenosine, the ADA substrate and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics in these CAR-Ts reveal alterations of global gene expression and metabolic signatures in both ADA- and PDK1- engineered CAR-T cells. Functional and immunological analyses demonstrate that ADA -OE increases proliferation and decreases exhaustion in α-CD19 and α-HER2 CAR-T cells. ADA-OE improves tumor infiltration and clearance by α-HER2 CAR-T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR-T cells, and reveal potential targets for improving CAR-T based cell therapy.SynopsisThe authors identify the adenosine deaminase gene (ADA) as a regulatory gene that reprograms T cell metabolism. ADA-overexpression (OE) in α-CD19 and α-HER2 CAR-T cells increases proliferation, cytotoxicity, memory, and decreases exhaustion, and ADA-OE α-HER2 CAR-T cells have enhanced clearance of HT29 human colorectal cancer tumors in vivo .

| S-EPMC10055032 | biostudies-literature

Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.

Project description:Immune evasion is a critical step of cancer progression that remains a major obstacle for current T cell-based immunotherapies. Hence, we investigated whether it is possible to genetically reprogram T cells to exploit a common tumor-intrinsic evasion mechanism whereby cancer cells suppress T-cell function by generating a metabolically unfavorable tumor microenvironment (TME). In an in silico screen, we identified ADA and PDK1 as metabolic regulators. We then showed that overexpression (OE) of these genes enhanced the cytolysis of CD19-specific chimeric antigen receptor (CAR) T cells against cognate leukemia cells, and conversely, ADA or PDK1 deficiency dampened this effect. ADA-OE in CAR T cells improved cancer cytolysis under high concentrations of adenosine, the ADA substrate, and an immunosuppressive metabolite in the TME. High-throughput transcriptomics and metabolomics analysis of these CAR T cells revealed alterations of global gene expression and metabolic signatures in both ADA- and PDK1-engineered CAR T cells. Functional and immunologic analyses demonstrated that ADA-OE increased proliferation and decreased exhaustion in CD19-specific and HER2-specific CAR T cells. ADA-OE improved tumor infiltration and clearance by HER2-specific CAR T cells in an in vivo colorectal cancer model. Collectively, these data unveil systematic knowledge of metabolic reprogramming directly in CAR T cells and reveal potential targets for improving CAR T-cell therapy.

| S-EPMC10527769 | biostudies-literature

CDK4/6 inhibitors modulate the ubiquitin proteosomal pathway by suppression of the ubiquitin conjugating enzymes UBE2C/S/T

Project description:Despite significant improvement in therapeutic development in the past decades, breast cancer remains a formidable cause of death for women worldwide. The hormone positive subtype (HR(+)) (also known as luminal type) is the most prevalant category of breast cancer, comprising ~70% of patients. The clinical success of the three CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has revolutionzied the treatment of choice for metastatic HR(+) breast cancer. Accumulating evidence demonstrate that the properties of CDK4/6 inhibitors extend beyond inhibition of the cell cycle, including modulation of immune function , sensitizing PI3K inhibitors, metabolism reprogramming , kinome rewiring, modulation of the proteosome, and many others. The ubiquitin–proteasome pathway (UPP) is a crucial cellular proteolytic system that maintains the homeostasis and turnover of proteins. By transcriptional profiling of the HR(+) breast cancer cell lines treated with the three CDK4/6 inhibitors, we have uncovered a novel mechanism that demonstrate the CDK4/6 inhibitors suppress the expression of three ubiquitin conjugating enzymes UBE2C, UBE2S, UBE2T. These three E2 enzymes modulate a number of E3 ubiquitin ligases, including the APC/C complex which plays a role in G1/S progression. Our study provide a novel link between CDK4/6 inhibitor and UPP which could have important implications in cancer biology.

2022-04-23 | GSE201113 | GEO

CDK4/6 inhibitors modulate the ubiquitin proteosomal pathway by suppression of the ubiquitin conjugating enzymes UBE2C/S/T

Project description:CDK4/6 inhibitors modulate the ubiquitin proteosomal pathway by suppression of the ubiquitin conjugating enzymes UBE2C/S/T

| PRJNA828445 | ENA

Tibetan sheep microbiome and metabolomics

Project description:Tibetan sheep microbiome and metabolomics

| PRJEB36249 | ENA