He and Xu et al. showed that in mice with B16F10 melanoma or 4T1 breast cancer, high-salt diet (HSD) reduced tumor growth and prolonged survival without apparent toxicity. In tumors, HSD increased salt storage and osmotic stress, increased proinflammatory cytokines, converted PMN-MDSCs from immunosuppressive to proinflammatory, and reduced the percentage of M-MDSCs by promoting their differentiation into proinflammatory macrophages via p38/MAPK-dependent activation of NFAT5. HSD also reduced Tregs and increased Th17, CD4+, and CD8+ T cells within tumors. HSD synergized with anti-PD-1 to further reduce tumor growth.
Contributed by Anna Scherer
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.
Author Info: (1) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. State Key La
Author Info: (1) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR. Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. (2) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. (3) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR. (4) State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR. (5) Department of Burn and Plastic Surgery, First Affiliated Hospital of Wannan Medical College, Jinghu District, Wuhu City, Anhui Province, 241000, China. (6) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. (7) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. jfzhang@nju.edu.cn. (8) State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau SAR. cmwang@umac.mo. (9) State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and Medical School of Nanjing University, 163 Xianlin Avenue, Nanjing, 210093, China. leidong@nju.edu.cn.
