| First Author | Geiger R | Year | 2016 |
| Journal | Cell | Volume | 167 |
| Issue | 3 | Pages | 829-842.e13 |
| PubMed ID | 27745970 | Mgi Jnum | J:243512 |
| Mgi Id | MGI:5908764 | Doi | 10.1016/j.cell.2016.09.031 |
| Citation | Geiger R, et al. (2016) L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity. Cell 167(3):829-842.e13 |
| abstractText | 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. |
