At this point, anyone who is not aware that high salt intake is a risk factor for hypertension and cardiovascular disease might have literally been living under a rock for the past few decades. However, what is less well-known is that that too much salt may impact autoimmunity, as recent studies have revealed that a high salt diet could change the immune cell balance towards a more aggressive state and worsen autoimmunity. Interestingly though, while these shifts in the immune cell balance—though detrimental in autoimmune conditions—could, in theory, be useful in anticancer immune therapies to improve immune attacks against tumor cells.

New evidence from an international team of investigators, led by scientists at the University of Hasselt, Belgium, shows that high salt intake inhibits tumor growth in mice. The effect seems to be due to a change in the function of certain immune cells that play a critical role in cancer immunity. Findings from the new study—published recently in Frontiers in Immunology through an article titled “High Salt Inhibits Tumor Growth by Enhancing Anti-tumor Immunity”—might be beneficial for improving anticancer immunotherapies in the future.

The research team found that a high salt diet inhibited tumor growth in two independent mouse models. Moreover, the scientists showed that this effect seemed to be related to a change in the functions of certain immune cells, so-called myeloid-derived suppressor cells (MDSCs). MDSCs are believed to hinder other immune cells to efficiently attack and eliminate tumor cells.

“We showed that high salt significantly inhibited tumor growth in two independent murine tumor transplantation models,” the authors wrote. “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 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.”

When the researchers mimicked a salty environment in cell culture, they observed a functional change in MDSCs. The cells were less capable to inhibit other immune cells. A similar modulatory effect of high salt conditions on MDSCs was observed with cells isolated from human cancer patients. Furthermore, if these cells were depleted, the effect of a high salt diet on tumor growth in mice was undone.

“High salt conditions seem to inhibit tumor growth by enabling more pronounced anti-tumor immunity through the functional modulation of MDSCs,” the authors noted.

MDSCs are suspected to be an important mechanism that prevents an efficient immune attack against tumors in anticancer immunotherapies. The underlying molecular mechanism that blocks the function of these cells could, therefore, have therapeutic potential. However, since high salt intake is suspected to be a risk factor for gastric cancer in humans, the findings of this study and molecular mechanisms behind them must be carefully analyzed in future studies.

“The findings are highly interesting, and we were surprised to see such an effect on tumor growth just by increasing the salt in the diet,” concluded senior study investigator Markus Kleinewietfeld, PhD, group leader at VIB-UHasselt. “However, future studies are needed to fully understand the effect and the detailed underlying molecular mechanisms behind to judge its therapeutic potential for anticancer immunotherapies.”

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