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.
Highlights
The balance between pro- and anti-inflammatory cells and signals is critical for preserving immune homeostasis and a disturbed immune cell balance is believed to contribute to autoimmunity and cancer
We first applied a protocol previously used in models of hypertension and autoimmunity by pre-feeding mice with a 4% NaCl containing chow and 1% NaCl in the drinking water compared to a control diet before tumor inoculation (Figure 1A) [1, 4]
Besides implications in cardiovascular pathologies, recent data have clearly shown that high salt intake could profoundly modulate the immune system through direct and indirect mechanisms-mainly leading to shifts toward a pro-inflammatory milieu [6, 7]
Summary
The balance between pro- and anti-inflammatory cells and signals is critical for preserving immune homeostasis and a disturbed immune cell balance is believed to contribute to autoimmunity and cancer. Recent data have demonstrated that a high salt diet (HSD) could influence the immune cell balance toward a pro-inflammatory state, where the induction of pro-inflammatory cells, such as T helper 17 cells (TH17) and M1-like macrophages is promoted and the function of anti-inflammatory cells, such as M2-like macrophages and regulatory T cells (Tregs) is impaired [1,2,3,4]. The pro-inflammatory effects of a HSD are believed to be associated with autoimmune diseases like e.g., multiple sclerosis (MS) and inflammatory bowel diseases (IBD) [7]. These pro-inflammatory effects of high salt on the immune cell balance raise the question if high salt conditions could affect anti-tumor immunity and cancer
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