Every athlete knows that magnesium (Mg2+) is important for well-functioning muscles. However, Mg2+ also plays an important role in cellular immunology, a fact which was largely unknown, just until recently. Mg2+ deficiency is the most underdiagnosed electrolyte abnormality and has been associated with a variety of diseases including infections and cancer. Therefore, the research team with Jonas Lötscher aimed to investigate the biological relevance of extracellular magnesium for immune cells.

In experimental tumor mouse models, the awardee has shown that CD8+ T cells – a specialized type of immune cells – require an Mg2+ -rich environment for activation and efficient elimination of cancer cells. Specifically, Mg2+ is important for the function of LFA-1. This cell surface molecule acts as a docking site and plays a key role in T cell activation. Mg2+ application into the tumors also resulted in an increased efficacy of so-called checkpoint inhibitors. These therapeutic agents support the immune system in attacking cancer cells. Based on these results, the young scientist retrospectively assessed the relation between serum Mg2+ levels and therapeutic outcomes in patients with lung cancer as well as B cell lymphoma who participated in a clinical trial with immune checkpoint inhibitors or CAR T cell therapy respectively. The retrospective analysis of both patient groups showed that the survival of patients was significantly reduced when they exhibited low serum Mg2+ levels.

The observation that Mg2+ is essential for efficient T cell function may be highly relevant in the context of modern cancer immunotherapies. The results offer the opportunity to develop novel preventive or therapeutic strategies in the battle against infections and cancer. The findings of Jonas Lötscher and colleagues have potential to be translated directly into clinical practice and clinical trials are planned.

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function. Jonas Lötscher, Adrià-Arnau Martí I Líndez, Nicole Kirchhammer, Elisabetta Cribioli, Greta Maria Paola Giordano Attianese, Marcel P Trefny, Markus Lenz, Sacha I Rothschild, Paolo Strati, Marco Künzli, Claudia Lotter, Susanne H Schenk, Philippe Dehio, Jordan Löliger, Ludivine Litzler, David Schreiner, Victoria Koch, Nicolas Page, Dahye Lee, Jasmin Grählert, Dmitry Kuzmin, Anne-Valérie Burgener, Doron Merkler, Miklos Pless, Maria L Balmer, Walter Reith, Jörg Huwyler, Melita Irving, Carolyn G King, Alfred Zippelius, Christoph Hess. Cell. 2022 Feb 17;185(4):585-602.e29.