意大利IRCCS医院Enrico Lugli团队发现，NaCl可增强癌症免疫疗法中CD8⁺ T细胞的效应功能。该项研究成果于2024年8月28日在线发表在《自然—免疫学》杂志上。

研究人员发现，氯化钠（NaCl）能够对抗T细胞功能失调，从而促进癌症的退化。在CD8⁺ T细胞培养过程中补充NaCl，能够诱导效应分化、IFN-γ的产生以及细胞毒性，同时维持负责干样可塑性的基因网络。因此，将肿瘤特异性T细胞进行过继转移后，在人源化小鼠模型中表现出更强的抗肿瘤免疫力。

在小鼠中，高盐饮食通过抑制终末分化并增强CD8⁺ T细胞的效应能力，依赖CD8⁺ T细胞减少了实验性肿瘤的生长。在机制上，NaCl增强了谷氨酰胺的消耗，这对于转录、表观遗传和功能的重新编程至关重要。在人类中，NaCl诱导的CD8⁺ T细胞在肿瘤中进行抗原识别，并预测对检查点抑制免疫疗法的良好反应。因此，NaCl代谢是CD8⁺ T细胞效应功能的调节因子，对癌症免疫疗法具有潜在影响。

据了解，CD8⁺ T细胞能够控制肿瘤，但在肿瘤微环境中不可避免地会功能失调。

附：英文原文

Title: NaCl enhances CD8+ Tcell effector functions in cancer immunotherapy

Author: 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

Issue&Volume: 2024-08-28

Abstract: CD8+ Tcells control tumors but inevitably become dysfunctional in the tumor microenvironment. Here, we show that sodium chloride (NaCl) counteracts Tcell dysfunction to promote cancer regression. NaCl supplementation during CD8+ Tcell 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 Tcells 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+ Tcell-dependent manner by inhibiting terminal differentiation and enhancing the effector potency of CD8+ Tcells. Mechanistically, NaCl enhanced glutamine consumption, which was critical for transcriptional, epigenetic and functional reprogramming. In humans, CD8+ Tcells 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+ Tcell effector function, with potential implications for cancer immunotherapy.

DOI: 10.1038/s41590-024-01923-9

Source: https://www.nature.com/articles/s41590-024-01923-9