Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

In Vivo CRISPR Screens Identify SLC1A5 as a Metabolic Checkpoint for Cancer Immunotherapy [ATAC]

ABSTRACT: Tumor cells often evade immune pressure via metabolic reprogramming, yet the key metabolic regulators orchestrating this process remain poorly defined. Here, using in vivo metabolic CRISPR screening under distinct immune pressures, we identified tumor cell–derived solute carrier family 1 member 5 (SLC1A5) as a critical metabolic node that sustains an immunosuppressive tumor microenvironment (TME). SLC1A5-mediated glutamine metabolism in tumor cells modulates CD8 T cell infiltration and effector function, reshaping tumor response to immune checkpoint blockade therapy. Mechanistically, glucose deprivation up-regulated SLC1A5 isoforms in tumor cells, enhancing glutamine uptake and metabolic flux remodeling to reset intracellular metabolic homeostasis. This program suppressed inflammatory tumor cell differentiation characterized by cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway activation, reducing interferon-β secretion and impairing CD8 immunity. These findings define a glutamine-fueled metabolic program as a critical barrier to tumor immunogenicity, positioning SLC1A5 as a metabolic immune checkpoint with therapeutic relevance.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE335904 | GEO | 2026/06/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE335904_RAW.tar	Raw
	filelist.txt	Txt

Items per page:

1 - 3 of 3

Similar Datasets

In Vivo CRISPR Screens Identify SLC1A5 as a Metabolic Checkpoint for Cancer Immunotherapy

Project description:Tumor cells often evade immune pressure via metabolic reprogramming, yet the key metabolic regulators orchestrating this process remain poorly defined. Here, using in vivo metabolic CRISPR screening under distinct immune pressures, we identified tumor cell–derived solute carrier family 1 member 5 (SLC1A5) as a critical metabolic node that sustains an immunosuppressive tumor microenvironment (TME). SLC1A5-mediated glutamine metabolism in tumor cells modulates CD8 T cell infiltration and effector function, reshaping tumor response to immune checkpoint blockade therapy. Mechanistically, glucose deprivation up-regulated SLC1A5 isoforms in tumor cells, enhancing glutamine uptake and metabolic flux remodeling to reset intracellular metabolic homeostasis. This program suppressed inflammatory tumor cell differentiation characterized by cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS–STING) pathway activation, reducing interferon-β secretion and impairing CD8 immunity. These findings define a glutamine-fueled metabolic program as a critical barrier to tumor immunogenicity, positioning SLC1A5 as a metabolic immune checkpoint with therapeutic relevance.

2026-06-23 | GSE334465 | GEO

In Vivo CRISPR Screens Identify SLC1A5 as a Metabolic Checkpoint for Cancer Immunotherapy [CUT&Tag]

2026-06-23 | GSE335906 | GEO

SLC1A5 prevents aortic aneurysm and dissection by glutaminolytic-epigenetic orchestration of vascular smooth muscle cell homeostasis [RNA-seq]

Project description:Glutamine is carried into and out of cells by glutamine transporters such as SLC1, SLC7 and SLC38 families, and cytoplasmic glutamine subsequently catabolized to glutamate that provides biosynthetic precursors. To identify the candidate glutamine transporters or glutamate metabolism regulators that contributed to the pathogenesis of Aortic aneurysm and dissection (AAD), we used RNA sequencing analysis in Ang II perfusion-induced AAD in Apoe-/- mice and discovered that several key genes associated with glutamine transports and metabolism were considerably reduced in AAD, particularly Slc1a5.

2026-03-15 | GSE309259 | GEO

Effect of SLC1A5 overexpression on T cell metabolism and function

Project description:Glutamine-dependence of cancer cells reduces local glutamine availability, which hinders anti-tumor T-cell functionality and facilitates immune evasion. We thus speculated that glutamine deprivation might be limiting efficacy of CAR T-cell therapies in cancer patients. We have seen that antigen-specific T cells are unable to proliferate or produce IFN-γ in response to antigen stimulation when glutamine concentration is limited. Using multiple myeloma (MM) as a glutamine-dependent disease model, we found that murine CAR-T cells selectively targeting BCMA in MM cells were sensitive to glutamine deprivation. However, CAR-T cells engineered to increase glutamine uptake by expression of the glutamine transporter Asct2 exhibited enhanced proliferation and responsiveness to antigen stimulation, increased production of IFN-, and heightened cytotoxic activity, even under conditions of low glutamine concentration. Mechanistically, Asct2 overexpression reprogrammed CAR-T cell metabolic fitness, improving basal oxygen consumption rate and glycolytic function that enhanced CAR-T cell persistence in vivo. Accordingly, expression of Asct2 increased the efficacy of BCMA CAR-T cells in syngeneic and genetically-engineered mouse models of MM, which prolonged mouse survival. In patients, reduced expression of Asct2 by MM cells predicted poor outcome to combined immunotherapy and BCMA-CAR T-cell therapy. Our results indicate that reprogramming glutamine metabolism may enhance anti-tumor CAR T-cell functionality in multiple myeloma. This approach may also be effective for other cancers that depend on glutamine as a key energy source and metabolic hallmark.

2025-08-21 | GSE299766 | GEO

A Glutamine Antagonist Prodrug Reprograms Dendritic Cells to Enhance Colorectal Cancer Immunotherapy

Project description:The tumor microenvironment (TME) imposes profound metabolic and immunosuppressive barriers that compromise the functionality of immune cells and limit effective anti-tumor responses. A hallmark of many tumors is their heightened dependency on glutamine as a metabolic substrate, which leads to glutamine depletion within the TME. This glutamine scarcity impairs the function of dendritic cells (DCs), resulting in defective antigen presentation and diminished activation of CD8⁺ cytotoxic T cells. Here, we report T26, a bifunctional immunometabolic prodrug composed of JHU083 (a glutamine antagonist) and MSA-2 (a STING agonist), designed to restore DC functionality and enhance anti-tumor immunity. T26 effectively suppresses tumor growth in colorectal cancer (CRC) models by reprogramming the TME toward a more immunostimulatory state. Mechanistically, T26 promotes DC maturation, enhances antigen presentation, and facilitates robust CD8⁺ T cell responses, leading to durable tumor suppression. Importantly, DC depletion experiments demonstrate that the anti-tumor efficacy of T26 is critically dependent on DC activation. Moreover, T26 reprograms tumor-derived extracellular vesicles (EVs), enhancing their capacity to transmit immunostimulatory signals and support CD8⁺ T cell–mediated cytotoxicity. In addition, T26 exhibits strong synergistic effects when combined with standard chemotherapy, immune checkpoint blockade, and anti-angiogenic therapy, further potentiating therapeutic efficacy. Collectively, these findings position T26 as a promising candidate for combination cancer immunotherapy, offering a dual-acting strategy that overcomes metabolic suppression and immune evasion in the TME to improve treatment outcomes.

2026-03-06 | GSE296658 | GEO

Effect of depletion of SLC1A5 on gene expression in T98G glioma cell line.

Project description:To investigate the function of SLC1A5 in glioma cells, we establishedT98G cell line in which SLC1A5 has been knocked down by shRNA.

2023-12-31 | GSE224742 | GEO

Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

Project description:Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade

| PRJNA327201 | ENA

Dietary Glutamine Supplementation Mitigates Age-Associated Cardiac Decline by Restricting H3K27me3

Project description:Epigenetic alterations are central drivers of cardiovascular aging, with histone modifications regulating gene expression through chromatin remodeling and changes in DNA accessibility. However, the mechanisms underlying these epigenetic shifts in the aging heart remain poorly defined. Here, we identify an age-associated accumulation of the repressive histone mark H3K27me3 in the myocardium of mice and humans, implicating this modification in myocardial aging. Elevated H3K27me3 was associated with impaired glutamine metabolism, driven by reduced expression of the amino acid transporter SLC1A5. Clinically, low circulating glutamine levels correlated with increased heart failure incidence, and genetic variants in SLC1A5 were linked to heightened cardiovascular disease risk. Mechanistically, elevated myocardial H3K27me3 suppressed cardiomyocyte autophagy and induced metabolic reprogramming, thereby promoting age-related myocardial dysfunction. Dietary glutamine supplementation in aged mice reduced H3K27me3 accumulation and improved myocardial function. Collectively, these findings identify a novel epigenetic mechanism underlying cardiac aging and highlight the glutamine–SLC1A5 axis as a potential therapeutic target for preserving myocardial function with age.

2026-02-06 | GSE317412 | GEO

SLC1A5 prevents aortic aneurysm and dissection by glutaminolytic-epigenetic orchestration of vascular smooth muscle cell homeostasis [CUT&Tag]

Project description:In this study, we found that H3K9ac level were reduced both in vitro (Slc1a5 knockdown VSMCs) and in vivo (Slc1a5 knockout mice). To further investigate the potential functional significance that SLC1A5-mediated H3K9ac contributed to the pathogenesis of aortic aneurysm and dissection (AAD), we performed genome-wide cleavage under targets and tagmentation (CUT&Tag) analysis to identify candidate genes regulated by H3K9ac (CST, 9649S) in Slc1a5 knockdown mouse VSMCs. Following CUT&Tag, H3K9ac associated DNAs were amplified using non-biased conditions, labeled, and sequenced with Illumina novaseq Xplus.

2026-03-17 | GSE325132 | GEO

KrasG12D/+ co-mutation alters the transcriptional landscape of lung adenocarcinoma

Project description:The tumor microenvironment (TME) contains a rich source of nutrients that sustain cell growth and ultimately facilitate tumor progression. The availability of glucose and glutamine in the TME are essential for the development and activation of effector T cells that exert anti-tumor function. Recently, inhibition of glutaminase, the enzyme that hydrolyzes glutamine to glutamate, has garnered interest as an approach to both decrease tumor metabolism and growth, while increasing available glutamine in the TME for effector T cells. Checkpoint blockade immunotherapy unleashes anti-tumor effector capabilities of T cells, and although there are good responses in many solid tumors, a significant proportion of patients respond poorly. In lung adenocarcinoma, response to immunotherapy is reported to be impaired in KRAS-mutant patients harboring concurrent KEAP1 and STK11/Lkb1 mutations. To investigate the metabolism and immune microenvironment of KRAS-mutant lung adenocarcinoma, we generated a series of murine models that reflect the KEAP1 and STK11/Lkb1 mutational landscape seen in patients. Here we show increased glutamate abundance in the Lkb1-deficient TME associated with CD8 T cell activation in response to anti-PD1 checkpoint immunotherapy. Combination treatment with the glutaminase inhibitor CB-839 inhibited clonal expansion and cytotoxic activation of tumor-infiltrating CD8 T cells. Thus, CD8 T cells exposed to checkpoint immunotherapy have a dependence on glutamine and reliance on glutaminase activity and are negatively impacted by the glutaminase inhibitor in this highly activated state. Therefore, we discern that the combination of immunotherapy and glutaminase inhibition is not efficacious for CD8 T cell activation in the tumor microenvironment.

2022-05-02 | GSE193895 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data