L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
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Date
2016-10-20
Publication Type
Journal Article
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yes
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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 anti-tumor responses.
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published
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Journal / series
Volume
167 (3)
Pages / Article No.
829 - 8420000000000000
Publisher
Cell Press
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Edition / version
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Date collected
Date created
Subject
Cancer immunotherapy; L-arginine; LiP-MS; Metabolism; Metabolite sensing; Metabolome; Proteome; T cell; T cell survival
Organisational unit
03713 - Sauer, Uwe / Sauer, Uwe
03927 - Picotti, Paola / Picotti, Paola
03856 - Lanzavecchia, Antonio (emeritus)
08839 - Zamboni, Nicola (Tit.-Prof.)