New paper by the Lanzavecchia Lab on the Dietary intake of arginine
on Thursday, October 13, 2016
A study led by researchers from the Institute for Research in Biomedicine (IRB) affiliated to the Università della Svizzera italiana (USI), shows that L-arginine, an amino acid that is consumed through diet, can boost the activity of a particular type of immune cells, so called T cells. When the levels of L-arginine are increased the metabolism of these cells is re-organized and the cells survive longer and are more effective in fighting tumors. These findings are published in the renowned scientific journal Cell and open up new ways to improve T cell therapies against cancer.
Researchers looked for patterns in the large datasets that they generated and identified the arginine metabolism as a potential target to modulate T cell activity.
T cells play crucial roles in the immune defense against viruses, bacteria and cancer cells. A long sought-after goal of immunologists is to tailor the activity and effectiveness of T cells to modulate the immune response. To explore the possibility that the activity of T cells can be regulated by components of our diet, the researchers systematically analyzed fluctuations of metabolic pathways in T cells following activation. For this, Roger Geiger, a postdoctoral fellow in the laboratory of Antonio Lanzavecchia (IRB Bellinzona) teamed up with the research groups of Nicola Zamboni (ETH Zürich) and Matthias Mann (MPI Munich) that are specialized in mass spectrometry-based technologies for the analysis of hundreds of metabolites and thousands of proteins within a cell. Based on this high-resolution analysis, the arginine metabolism was identified as a potential point for therapeutic intervention. This possibility was tested in the laboratory of Federica Sallusto (IRB Bellinzona) and led to the discovery that orally administered L-arginine endowed T cells with a higher survival capacity and a better effectiveness against tumors. To understand the underlying molecular mechanism, the researchers collaborated with another team headed by Paola Picotti (ETH Zürich) that developed a method for the identification of proteins that interact with metabolites. Using this approach three proteins were identified that sense increased L-arginine levels and participate in the remodeling of T cells toward increased survival.
The inset of a T cell (in blue) illustrates how L-arginine affects metabolic pathways and acts on receptors in the nucleus that endow T cells with a higher survival capacity. When these T cells enter a tumor they show increased activity to destroy tumor cells.
Roger Geiger, first and co-corresponding author of the paper says: “It is truly fascinating that a single metabolite can influence the properties of T cell in such a dramatic way”.
Federica Sallusto, a senior co-author in the study says: “We obtained proof of principle that T cells exposed to elevated L-arginine concentrations may function better in fighting against tumors. These finding may lead to improved cellular immunotherapies”.
Antonio Lanzavecchia, director of the IRB and Professor at ETH Zürich says: “This study demonstrates how the global analysis of proteins and metabolites in immune cells can generate hypotheses that open up new ways to enhance the immune response”.
Geiger et al. “L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity”
Advance Online Publication (AOP) on http://www.cell.com/cell/newarticles
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