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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords T(h)17 Cells; Expression; Activation; Transcription; Induction; Transport; Residency; Tissues; Binding; Single
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 1529-2908
e-ISSN 1529-2916
Journal Nature Immunology
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Research Unit BioGeoChemistry and Analytics (BGC)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Environmental Sciences
PSP Element(s) G-504800-002
Grants Carl-Zeiss-Stiftung (Carl Zeiss Foundation)
DOI 10.1038/s41590-024-01918-6
WOS ID 001303713300002
Scopus ID 85202603642
PubMed ID 39198632
Erfassungsdatum 2024-09-04
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