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High-salt diet inhibits tumour growth in mice via regulating myeloid-derived suppressor cell differentiation

Wei He, Jinzhi Xu, Ruoyu Mu, Qiu Li, Dalun Lv, Zhen Huang, Junfeng Zhang, Chunming Wang, Lei Dong

2020Nature Communications97 citationsDOIOpen Access PDF

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.

Topics & Concepts

Myeloid-derived Suppressor CellImmune systemCancer researchSuppressorp38 mitogen-activated protein kinasesSpleenPhenotypeCell growthImmunologyCancer cellBiologyCancerChemistryCell biologyKinaseProtein kinase AInternal medicineMedicineBiochemistryGeneTherapeutic Uses of Natural ElementsInflammation biomarkers and pathwaysImmune cells in cancer