Publications by authors named "Elizabeth G Hunt"

The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor-infiltrating T cells (TILs), hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors.

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Unlabelled: Protein synthesis supports robust immune responses. Nutrient competition and global cell stressors in the tumor microenvironment (TME) may impact protein translation in T cells and antitumor immunity. Using human and mouse tumors, we demonstrated here that protein translation in T cells is repressed in solid tumors.

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The endoplasmic reticulum (ER) is a large continuous membranous organelle that plays a central role as the hub of protein and lipid synthesis while the mitochondria is the principal location for energy production. T cells are an immune subset exhibiting robust dependence on ER and mitochondrial function based on the need for protein synthesis and secretion and metabolic dexterity associated with foreign antigen recognition and cytotoxic effector response. Intimate connections exist at mitochondrial-ER contact sites (MERCs) that serve as the structural and biochemical platforms for cellular metabolic homeostasis through regulation of fission and fusion as well as glucose, Ca, and lipid exchange.

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Article Synopsis
  • Mitochondrial membrane potential (ΔΨm) serves as a key indicator of mitochondrial function, and this study aimed to quantify its variability among different human cell types.
  • The researchers utilized a dual microscopy method to evaluate the relative and absolute measurements of ΔΨm in unsynchronized cancer cells, cells synchronized in specific phases of the cell cycle, and human fibroblasts.
  • Findings revealed that cancer cells exhibit greater heterogeneity in ΔΨm than fibroblasts, with this variability being influenced by internal mitochondrial factors rather than external cell cycle phases or membrane potential differences.
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Statins, widely used to treat hypercholesterolemia, inhibit the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme of cholesterol (Chol) synthesis. Statins have been also reported to slow tumor progression. In cancer cells, ATP is generated both by glycolysis and oxidative phosphorylation.

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