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L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

MPS-Authors
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Rieckmann,  Jan C.
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Meissner,  Felix
Meissner, Felix / Experimental Systems Immunology, Max Planck Institute of Biochemistry, Max Planck Society;

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Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Geiger, R., Rieckmann, J. C., Wolf, T., Basso, C., Feng, Y., Fuhrer, T., et al. (2016). L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell, 167(3), 829-842. doi:10.1016/j.cell.2016.09.031.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-1AD1-0
Abstract
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 antitumor responses.