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

Cell, 2016-10, Vol.167 (3), p.829-842.e13 [Peer Reviewed Journal]

2016 The Author(s) ;Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved. ;2016 The Author(s) 2016 ;ISSN: 0092-8674 ;EISSN: 1097-4172 ;DOI: 10.1016/j.cell.2016.09.031 ;PMID: 27745970

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Title:
L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity
Author: Geiger, Roger ; Rieckmann, Jan C. ; Wolf, Tobias ; Basso, Camilla ; Feng, Yuehan ; Fuhrer, Tobias ; Kogadeeva, Maria ; Picotti, Paola ; Meissner, Felix ; Mann, Matthias ; Zamboni, Nicola ; Sallusto, Federica ; Lanzavecchia, Antonio
Subjects: Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Arginine - metabolism ; cancer immunotherapy ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; DNA-Binding Proteins - metabolism ; Gene Knockout Techniques ; Glycolysis ; Humans ; Immunologic Memory ; Immunomodulation ; L-arginine ; LiP-MS ; Lymphocyte Activation ; Melanoma, Experimental - immunology ; metabolism ; metabolite sensing ; Metabolome ; Mice ; Mice, Inbred BALB C ; Oxidative Phosphorylation ; Proteome ; Skin Neoplasms - immunology ; T cell ; T cell survival ; Transcription Factors - metabolism ; Transcription, Genetic
Is Part Of: Cell, 2016-10, Vol.167 (3), p.829-842.e13
Description: 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. [Display omitted] •Dataset on dynamic metabolome/proteome profiles of activated human naive T cells•Intracellular L-arginine levels regulate several metabolic pathways in T cells•T cells with increased L-arginine display enhanced survival and anti-tumor activity•LiP-MS identified proteins that are structurally modified by high L-arginine levels Metabolomic and proteomic profiling unveil intracellular L-arginine as a crucial regulator of metabolic fitness, survival capacity, and anti-tumor activity of central memory T cells.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 0092-8674
EISSN: 1097-4172
DOI: 10.1016/j.cell.2016.09.031
PMID: 27745970
Source: Cell Press Free Archives
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L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

2016 The Author(s) ;Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved. ;2016 The Author(s) 2016 ;ISSN: 0092-8674 ;EISSN: 1097-4172 ;DOI: 10.1016/j.cell.2016.09.031 ;PMID: 27745970

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