Lenz, Markus

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Lenz, Markus

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  • Publikation
    Magnesium sensing via LFA-1 regulates CD8+ T cell effector function
    (Cell Press, 2022) Lötscher, Jonas; Martí i Líndez, Adrià-Arnau; Kirchhammer, Nicole; Cribioli, Elisabetta; Giordano Attianese, Greta Maria Paola; Trefny, Marcel P.; Rothschild, Sacha I.; Strati, Paolo; Künzli, Marco; Lotter, Claudia; Schenk, Susanne H.; Dehio, Philippe; Löliger, Jordan; Litzler, Ludivine; Schreiner, David; Koch, Victoria; Page, Nicolas; Lee, Dahye; Grählert, Jasmin; Kuzmin, Dmitry; Burgener, Anne-Valérie; Merkler, Doron; Pless, Miklos; Balmer, Maria L.; Reith, Walter; Huwyler, Jörg; Irving, Melita; King, Carolyn G.; Zippelius, Alfred; Hess, Christoph; Lenz, Markus [in: Cell]
    The relevance of extracellular magnesium in cellular immunity remains largely unknown. Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesium to adopt its active conformation on CD8+ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming, immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly, magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen- and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engaging antibodies, and improved CAR T cell function. Clinically, low serum magnesium levels were associated with more rapid disease progression and shorter overall survival in CAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporates information on the composition of the microenvironment as a determinant of outside-in signaling activity. These findings conceptually link co-stimulation and nutrient sensing and point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.
    01A - Beitrag in wissenschaftlicher Zeitschrift