Researchers from the Institute for Research in Biomedicine (IRB) affiliated to the Universita della Svizzera italiana (USI), shows that L-arginine, which is an amino acid that is consumed through diet, can actually boost the activity of a particular type of immune cells, called T cells. The metabolism of these cells is organized and the cells survive longer and are more effective in fighting tumors when the levels of L-arginine are increased. The scientific journal Cell has published these findings and this opens up new ways to improve T cell therapies against cancer. Crucial roles in the immune defense against viruses, bacterial and cancer cells are played by T cells. A goal of immunologists is to tailor the activity and effectiveness of T cells trelaxo modulate the immune response. To explore this possibility the researchers systematically analyzed fluctuations of metabolic pathways in T cells following activation, according to Roger Geiger, a postdoctoral fellow in the lab of Antonio Lanzavecchia (IRB Bellinzona), teamed with the research groups of Nicola Zamboni (ETH Zurich) and Matthias Mann (MPI Munich) that are specialized in mass spectrometry-based technologies for the analysis of hundreds of metabolite and thousands of proteins within a cell.
The analysis revealed the arginine metabolism was identified as a potential point for therapeutic intervention. Federica Sallusto (IRB Bellinzona) tested in the lab and led to the discovery that orally administered L-arginine endowed T cells with a higher survival capacity and a better effectiveness against tumors.
The researchers then collaborated with another team headed by Paola Picotti (ETH Zurich) that developed a method for the identification of proteins that interact with metabolites. Three proteins were identified that sense increased L-arginine levels and participate in the remodeling of T cells toward increased survival.
Roger Geiger says it is truly fascinating that a single metabolite can influence the properties of T cell in such a dramatic way. Federica Sallusto believes they have obtained proof of principle that T cells with elevated L-arginine concentrations may function better in fighting against tumors that may lead to improved cellular immunotherapies. Director of the IRB and Professor at ETH Zurich, Antonio Lanzavecchia, reports 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.
–Dr Fredda Branyon