New Paper by the Lanzavecchia Lab
L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity.
Roger Geiger, Jan C. Rieckmann, Tobias Wolf, Camilla Basso, Yuehan Feng, Tobias Fuhrer, Maria Kogadeeva, Paola Picotti, Felix Meissner, Matthias Mann, Nicola Zamboni, Federica Sallusto, and Antonio Lanzavecchia.
Cell. 2016 Oct 20;167(3):829-842.e13. doi: 10.1016/j.cell.2016.09.031.
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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.