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Soll, D.* ; Chu, C.F.* ; Sun, S.* ; Lutz, V.* ; Arunkumar, M.* ; Gachechiladze, M.* ; Schäuble, S.* ; Alissa-Alkhalaf, M.* ; Nguyen, T.* ; Khalil, M.A.* ; Garcia-Ribelles, I.* ; Mueller, M.* ; Buder, K.* ; Michalke, B. ; Panagiotou, G.* ; Ziegler-Martin, K.* ; Benz, P.* ; Schatzlmaier, P.* ; Hiller, K.* ; Stockinger, H.* ; Luu, M.* ; Schober, K.* ; Moosmann, C.* ; Schamel, W.W.* ; Huber, M.* ; Zielinski, C.E.*

Sodium chloride in the tumor microenvironment enhances T cell metabolic fitness and cytotoxicity.

Nat. Immunol., DOI: 10.1038/s41590-024-01918-6 (2024)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The efficacy of antitumor immunity is associated with the metabolic state of cytotoxic T cells, which is sensitive to the tumor microenvironment. Whether ionic signals affect adaptive antitumor immune responses is unclear. In the present study, we show that there is an enrichment of sodium in solid tumors from patients with breast cancer. Sodium chloride (NaCl) enhances the activation state and effector functions of human CD8+ T cells, which is associated with enhanced metabolic fitness. These NaCl-induced effects translate into increased tumor cell killing in vitro and in vivo. Mechanistically, NaCl-induced changes in CD8+ T cells are linked to sodium-induced upregulation of Na+/K+-ATPase activity, followed by membrane hyperpolarization, which magnifies the electromotive force for T cell receptor (TCR)-induced calcium influx and downstream TCR signaling. We therefore propose that NaCl is a positive regulator of acute antitumor immunity that might be modulated for ex vivo conditioning of therapeutic T cells, such as CAR T cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter T(h)17 Cells; Expression; Activation; Transcription; Induction; Transport; Residency; Tissues; Binding; Single
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Zeitschrift Nature Immunology
Verlag Nature Publishing Group
Verlagsort Heidelberger Platz 3, Berlin, 14197, Germany
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Analytical BioGeoChemistry (BGC)
Förderungen Carl-Zeiss-Stiftung (Carl Zeiss Foundation)