Abstract
High-salt diets are associated with an elevated risk of autoimmune diseases, and immune dysregulation plays a key role in cancer development. However, the correlation between high-salt diets (HSD) and cancer development remains unclear. Here, we report that HSD increases the local concentration of sodium chloride in tumour tissue, inducing high osmotic stress that decreases both the production of cytokines required for myeloid-derived suppressor cells (MDSCs) expansion and MDSCs accumulation in the blood, spleen, and tumour. Consequently, the two major types of MDSCs change their phenotypes: monocytic-MDSCs differentiate into antitumour macrophages, and granulocytic-MDSCs adopt pro-inflammatory functions, thereby reactivating the antitumour actions of T cells. In addition, the expression of p38 mitogen-activated protein kinase-dependent nuclear factor of activated T cells 5 is enhanced in HSD-induced M-MDSC differentiation. Collectively, our study indicates that high-salt intake inhibits tumour growth in mice by activating antitumour immune surveillance through modulating the activities of MDSCs.
Highlights
High-salt diets are associated with an elevated risk of autoimmune diseases, and immune dysregulation plays a key role in cancer development
To investigate the effect of highsalt diets (HSD) on tumour growth, we established two grafted tumour models in female wild-type C57BL/6 and BABL/c mice: a mouse melanoma model established by implantation of B16F10 cells and a mouse mammary cancer model established by implantation of 4T1 cells
New evidence has demonstrated that high-level salt in vivo might contribute to cutaneous antibacterial defences, suggesting that HSD could be beneficial in skin defence[48]
Summary
High-salt diets are associated with an elevated risk of autoimmune diseases, and immune dysregulation plays a key role in cancer development. The two major types of MDSCs change their phenotypes: monocytic-MDSCs differentiate into antitumour macrophages, and granulocytic-MDSCs adopt pro-inflammatory functions, thereby reactivating the antitumour actions of T cells. Under high-salt stimulation, macrophages polarise towards a typical M1 phenotype, secreting more pro-inflammatory cytokines, reactive oxygen species (ROS) and nitric oxide synthase 2 (NOS2), and activating inflammasome-related pathways[8,9,10,11]. These findings suggest that high-salt intake promotes inflammation in various tissue microenvironments, which may induce inflammatory diseases such as rheumatoid arthritis (RA) and colitis[12,13]. Our results suggest that HSD, though recognised as an unhealthy dietary pattern, dramatically regulates the differentiation of MDSCs in the tumour niche, leading to the removal of local immune suppression and inhibition of tumour progression
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