1. L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.
- Author
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Geiger, Roger, Rieckmann, Jan C., Wolf, Tobias, Basso, Camilla, Feng, Yuehan, Fuhrer, Tobias, Kogadeeva, Maria, Picotti, Paola, Meissner, Felix, Mann, Matthias, Zamboni, Nicola, Sallusto, Federica, and Lanzavecchia, Antonio
- Subjects
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ARGININE metabolism , *T cells , *ANTINEOPLASTIC agents , *CELL metabolism , *METABOLOMICS , *GLYCOLYSIS - Abstract
Summary Metabolic activity is intimately linked to T cell fate and function. Using high-resolution mass spectrometry, we generated dynamic metabolome and proteome profiles of human primary naive T cells following activation. We discovered critical changes in the arginine metabolism that led to a drop in intracellular L-arginine concentration. Elevating L-arginine levels induced global metabolic changes including a shift from glycolysis to oxidative phosphorylation in activated T cells and promoted the generation of central memory-like cells endowed with higher survival capacity and, in a mouse model, anti-tumor activity. Proteome-wide probing of structural alterations, validated by the analysis of knockout T cell clones, identified three transcriptional regulators (BAZ1B, PSIP1, and TSN) that sensed L-arginine levels and promoted T cell survival. Thus, intracellular L-arginine concentrations directly impact the metabolic fitness and survival capacity of T cells that are crucial for anti-tumor responses. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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