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Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity

ABSTRACT: Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity

PROVIDER: PRJNA971134 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24492230.fastq.gz	Fastqsanger.gz
	SRR24492231.fastq.gz	Fastqsanger.gz
	SRR24492232.fastq.gz	Fastqsanger.gz
	SRR28502383_1.fastq.gz	Fastqsanger.gz
	SRR28502383_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity

Project description:The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is highly amenable to perturbation by the tumor microenvironment. It is therefore of tremendous interest to bypass immunosuppressive signaling in the tumor microenvironment and to identify factors that augment T cell immunometabolism, cytotoxic effector functions and eventually tumor killing. Whether ionic signals serve as aberrant immune signals and influence the adaptive human antitumor immune response is still largely unexplored. We demonstrate a significant enrichment of sodium in solid tumors of breast cancer patients, which leaves a transcriptomic imprint on intratumoral immune cells. Sodium chloride (NaCl) enhanced the activation state and effector functions of human CD8+ memory T cells. These functional alterations were associated with improved metabolic fitness, in particular with an increase in glycolysis and oxidative phosphorylation and overall nutrient uptake. These NaCl-induced effects translated into increased tumor cell killing in vitro and in a tumor mouse model in vivo. We therefore propose NaCl as a positive regulator of acute antitumor immunity, which could be harnessed for ex vivo conditioning of adoptively transferred T cells in the future.

2024-06-21 | GSE232149 | GEO

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and tumor killing

Project description:Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and tumor killing

| PRJNA971744 | ENA

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.

Project description:The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer. Sodium chloride (NaCl) enhances the activation state and effector functions of human CD8+ T cells, which is associated with enhanced metabolic fitness. These NaCl-induced effects translate into increased tumor cell killing in vitro and in vivo. Mechanistically, NaCl-induced changes in CD8+ T cells are linked to sodium-induced upregulation of Na+/K+-ATPase activity, followed by membrane hyperpolarization, which magnifies the electromotive force for T cell receptor (TCR)-induced calcium influx and downstream TCR signaling. We therefore propose that NaCl is a positive regulator of acute antitumor immunity that might be modulated for ex vivo conditioning of therapeutic T cells, such as CAR T cells.

| S-EPMC11436365 | biostudies-literature

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and tumor killing

Project description:To gain mechanistic insight into the effect of NaCl on CD8+ T cells, we explored the specific impact of NaCl on the bulk transcriptome of human memory CD8+ T cells.

2024-06-21 | GSE232365 | GEO

Sodium chloride generates anti-inflammatory Th17 cell responses but amplifies Th17 cell pathogenicity in pro-inflammatory cytokine microenvironments

Project description:T helper cells integrate signals from their microenvironment to acquire distinct specialization programs for efficient clearance of diverse pathogens or for immunotolerance. Ionic signals have recently been demonstrated to affect T cell polarization and function. Sodium chloride (NaCl) was proposed to accumulate in peripheral tissues upon dietary intake and to promote autoimmunity via the Th17 cell axis. Here we demonstrate that high NaCl conditions induced a stable, pathogen-specific, anti-inflammatory Th17 cell fate in human T cells in vitro. The p38/MAPK pathway, involving NFAT5 and SGK1, regulated FoxP3 and interleukin (IL)-17-expression in high-NaCl conditions. The NaCl-induced acquisition of an anti-inflammatory Th17 cell fate was confirmed in vivo in an experimental autoimmune encephalomyelitis (EAE) mouse model, which demonstrated strongly reduced disease symptoms upon transfer of T cells polarized in high NaCl conditions. However, NaCl was coopted to promote murine and human Th17 cell pathogenicity, if T cell stimulation occurred in a pro-inflammatory and TGF--low cytokine microenvironment. Taken together, our findings reveal a context-dependent, dichotomous role for NaCl in shaping Th17 cell pathogenicity. NaCl might therefore prove beneficial for the treatment of chronic inflammatory diseases in combination with cytokine-blocking drugs.

2020-04-15 | GSE148669 | GEO

Sodium chloride generates anti-inflammatory Th17 cell responses but amplifies Th17 cell pathogenicity in pro-inflammatory cytokine microenvironments

Project description:Sodium chloride generates anti-inflammatory Th17 cell responses but amplifies Th17 cell pathogenicity in pro-inflammatory cytokine microenvironments

| PRJNA625315 | ENA

Genome changes associated with a Zymomonas mobilis sodium acetate-tolerant mutant (AcR)

Project description:We report the genome changes associated with a Zymomonas mobilis sodium acetate-tolerant mutant (AcR). We used comparative genomics, transcriptomics, and genetics to show nhaA over-expression conferred sodium acetate (NaAc) tolerance in Z. mobilis. We observed a synergistic effect for sodium and acetate ions that enhanced toxicity against the wild-type strain (ZM4), which was not observed for similar concentrations of potassium and ammonium acetate under controlled laboratory conditions. We extended our studies and demonstrated that Saccharomyces cerevisiae sodium-proton antiporter genes contribute to NaAc tolerance for this important ethanologen. The application of classical and systems biology tools is a paradigm for industrial strain improvement and combines benefits of few a priori assumptions with detailed, rapid, mechanistic studies. Finally, our studies reinforce the idea that one obtains what one selects for in mutant screens and that a genetic system is important for industrial strain development. ZM4_ACr_NaCl_NaAc_study. Whole-genome expression profiles of exponential and stationary phase cells were analyzed for the wild-type Zymomonas mobilis ZM4 and the acetate-tolerant mutant AcR under 12g/L sodium acetate and same molar concentration of sodium chloride (8.55g/L) control conditions.

2010-05-05 | E-GEOD-18106 | biostudies-arrayexpress

TMC4 is a novel chloride channel involved in high-concentration salt taste sensation

Project description:Taste substances are received by taste receptors expressed in taste cells. “Salty taste” sensation is evoked when sodium and chloride ions are present together in the oral cavity. The presence of an epithelial cation channel that receives Na+ has previously been reported. However, no molecular entity involving Cl- receptors has been elucidated. We report the strong expression of transmembrane channel-like 4 (TMC4) in the circumvallate and foliate papillae projected to the glossopharyngeal nerve, mediating a high-concentration of NaCl. Electrophysiological analysis using HEK293T cells revealed that TMC4 was a voltage-dependent Cl- channel and the consequent currents were completely inhibited by NPPB, an anion channel blocker. This channel could be activated without an increase in intracellular calcium ion. TMC4 allowed permeation of organic anions including gluconate, but their current amplitudes at positive potentials were less than that of Cl-. Tmc4-deficient mice showed significantly weaker glossopharyngeal nerve response to high-concentration of NaCl than the wild-type littermates. These results indicated that TMC4 is a novel chloride channel that responds to high-concentration of NaCl.

2021-09-14 | GSE175806 | GEO

Herbivore-induced plant protein in honeydew enhances natural enemy fitness. Effect of honeydew on parasitoid fitness

Project description:The role of plant-derived food sources in plant-herbivore-carnivore interactions is an essential topic in basic ecology, and it is directly linked to the applied discipline of biological pest control. Honeydew, which phloem-feeding hemipteran insects excrete, constitutes a rich source of carbohydrates and proteins for beneficial insects in ecosystems. However, the quality of this plant-derived food source depends on its composition. Here we demonstrated that plant proteins in honeydew increase the fitness of a parasitic wasp (member of the third-trophic level).

2024-06-05 | PXD042138 | Pride

Tn-Seq of Benzalkonium Chloride Treated and Untreated Acinetobacter baumannii

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2018-01-23 | GSE96745 | GEO

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