High Salt Inhibits Tumor Growth by Enhancing Anti-tumor Immunity

Abstract

Excess salt intake could affect the immune system by shifting the immune cell balance toward a pro-inflammatory state. Since this shift of the immune balance is thought to be beneficial in anti-cancer immunity, we tested the impact of high salt diets on tumor growth in mice. Here we show that high salt significantly inhibited tumor growth in two independent murine tumor transplantation models. Although high salt fed tumor-bearing mice showed alterations in T cell populations, the effect seemed to be largely independent of adaptive immune cells. In contrast, depletion of myeloid-derived suppressor cells (MDSCs) significantly reverted the inhibitory effect on tumor growth. In line with this, high salt conditions almost completely blocked murine MDSC function in vitro . Importantly, similar effects were observed in human MDSCs isolated from cancer patients. Thus, high salt conditions seem to inhibit tumor growth by enabling more pronounced anti-tumor immunity through the functional modulation of MDSCs. Our findings might have critical relevance for cancer immunotherapy.

Dietary Salt Administration Decreases Enterotoxigenic Bacteroides fragilis (ETBF)-Promoted Tumorigenesis via Inhibition of Colonic Inflammation

“…A recent study showed that HSD enhanced the anti-tumor immunity of xenografted cancer cells (B16F10 melanoma cells and Lewis lung carcinoma cells) in Rag KO mice [40]. In this study, there were no significant differences in the proportions of monocytes/macrophages and NK cells in the tumor microenvironment compared to NSD-fed Rag KO mice bearing the cancer cells.…”

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

“…HSD-induced pro-inflammatory reactions in vivo. Emerging evidence suggests that high-salt conditions can modulate the functions and differentiation of immune cells 7,8,28 . To determine whether HSD influences the levels of the cytokines in serum and tumours, we measured cytokine levels in different tissues using a Proteome Profiler Mouse XL Cytokine Array (Ray Biothech).…”

“…On the other hand, new evidence has demonstrated that high-level salt in vivo might contribute to cutaneous antibacterial defences, suggesting that HSD could also be beneficial in skin defence 48 . A recent study also suggests its implication on tumour development 28 . In the present study, we found that HSD resulted in significant accumulation of salt in tumour tissue, modulated MDSC differentiation and function, restored immune surveillanc and eventually retarded tumour growth in mouse cancer models.…”

The Impact of Dietary Components on Regulatory T Cells and Disease

“…Besides, dietary nutrients and microbial metabolites alter the immune response by acting on different immune cell populations, challenging our aim to identify underlying immunological mechanisms targeted during dietary interventions. For instance, we have recently corroborated that high salt diet lead to alterations in T cell populations in murine tumor transplantation models (191). However, inhibition of tumor growth given by high salt diet was largely independent of T cells in these models.…”

“…However, inhibition of tumor growth given by high salt diet was largely independent of T cells in these models. Instead, high salt blocked the suppressive function of myeloid derived suppressor cells (MDSCs) in vitro and seems to promote thereby more pronounced anti-tumor immunity in vivo (191).…”