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Open AccessJournal ArticleDOI

Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

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TLDR
It is indicated that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+, and the efficacy of T cell-based therapies against chronic infectious diseases and cancer.
Abstract
Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of energy. After antigen encounter, T cells shift to a glycolytic metabolism to sustain effector function. It is unclear, however, whether changes in glucose metabolism ultimately influence the ability of activated T cells to become long-lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. Accordingly, enforcing glycolytic metabolism by overexpressing the glycolytic enzyme phosphoglycerate mutase-1 severely impaired the ability of CD8+ T cells to form long-term memory. Conversely, activation of CD8+ T cells in the presence of an inhibitor of glycolysis, 2-deoxyglucose, enhanced the generation of memory cells and antitumor functionality. Our data indicate that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+ T cells. These results have important implications for improving the efficacy of T cell–based therapies against chronic infectious diseases and cancer.

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Journal ArticleDOI

Gut microbiota mediates the inhibition of lymphopoiesis in dietary-restricted mice by suppressing glycolysis

TL;DR: This article showed that antibiotic ablation of the gut microbiota significantly rescued the inhibition of lymphopoiesis by Dietary Restriction (DR) in mice and showed that supplemental butyrate feeding in AL mice suppressed glycolysis in lymphoid cells and mimicked the inhibitory effect of LOPOiesis in DR mice.
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Association of Tumor Cell Metabolic Subtype and Immune Response With the Clinical Course of Hepatocellular Carcinoma.

TL;DR: In this paper , the potential association of tumor cell metabolism and immune cell tumor tumor infiltration with the clinical course of hepatocellular carcinoma (HCC) was evaluated, and a tumor microenvironment score system was constructed to evaluate its association with metabolic subtypes.
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The potential role of short chain fatty acids improving ex vivo T and CAR-T cell fitness and expansion for cancer immunotherapies

TL;DR: In this article , the authors summarized the ex vivo impact of short chain fatty acids, a group of gut microbiota derived metabolites, on T cell culture and expansion for immunotherapies.
Journal ArticleDOI

Insights into the relationship between persistent antibody secretion and metabolic programming - a question for single-cell analysis.

Klaus Eyer
- 12 Jun 2023 - 
TL;DR: In this article , metabolic programs influence and drive immune cell functions in general and plasma cell differentiation and longevity more specifically, summarizing the current knowledge on metabolic pathways and their influences on cellular fate.
Journal ArticleDOI

Metabolism along the life journey of T cells

Min Peng, +1 more
- 19 Jan 2023 - 
TL;DR: There has been an explosion of research into the metabolic control of T-cell responses, including glycolysis, lipid metabolism, and mitochondrial oxidative phosphorylation, and their mechanisms of action are starting to emerge as mentioned in this paper .
References
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Journal ArticleDOI

Lineage relationship and protective immunity of memory CD8 T cell subsets.

TL;DR: It is proposed that TCM and TEM do not necessarily represent distinct subsets, but are part of a continuum in a linear naive → effector → TEM → TCM differentiation pathway.
Journal ArticleDOI

The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation

TL;DR: Metabolic tracer analysis revealed a Myc-dependent metabolic pathway linking glutaminolysis to the biosynthesis of polyamines, which may represent a general mechanism for metabolic reprogramming under patho-physiological conditions.
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Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets

TL;DR: Teff and Treg were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation.
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