| Autor: |
Scirgolea, Caterina, Sottile, Rosa, De Luca, Marco, Susana, Alberto, Carnevale, Silvia, Puccio, Simone, Ferrari, Valentina, Lise, Veronica, Contarini, Giorgia, Scarpa, Alice, Scamardella, Eloise, Feno, Simona, Camisaschi, Chiara, De Simone, Gabriele, Basso, Gianluca, Giuliano, Desiree, Mazza, Emilia Maria Cristina, Gattinoni, Luca, Roychoudhuri, Rahul, Voulaz, Emanuele, Di Mitri, Diletta, Simonelli, Matteo, Losurdo, Agnese, Pozzi, Davide, Tsui, Carlson, Kallies, Axel, Timo, Sara, Martano, Giuseppe, Barberis, Elettra, Manfredi, Marcello, Rescigno, Maria, Jaillon, Sebastien, Lugli, Enrico |
| Zdroj: |
Nature Immunology; 20240101, Issue: Preprints p1-13, 13p |
| Abstrakt: |
CD8+T cells control tumors but inevitably become dysfunctional in the tumor microenvironment. Here, we show that sodium chloride (NaCl) counteracts T cell dysfunction to promote cancer regression. NaCl supplementation during CD8+T cell culture induced effector differentiation, IFN-γ production and cytotoxicity while maintaining the gene networks responsible for stem-like plasticity. Accordingly, adoptive transfer of tumor-specific T cells resulted in superior anti-tumor immunity in a humanized mouse model. In mice, a high-salt diet reduced the growth of experimental tumors in a CD8+T cell-dependent manner by inhibiting terminal differentiation and enhancing the effector potency of CD8+T cells. Mechanistically, NaCl enhanced glutamine consumption, which was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+T cells undergoing antigen recognition in tumors and predicting favorable responses to checkpoint blockade immunotherapy resembled those induced by NaCl. Thus, NaCl metabolism is a regulator of CD8+T cell effector function, with potential implications for cancer immunotherapy. |
| Databáze: |
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