L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity
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[1] Universita della Svizzera italiana
Universita della Svizzera italiana
Lugano, Suiza
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[2] Max Planck Institute
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- Localización: Cell, ISSN 0092-8674, Vol. 167, Nº. 3, 2016, págs. 829-842
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
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.
