A study by an international research team led by Professor Markus Kleinewietfeld (VIB-UHasselt) shows that high salt intake inhibits tumor growth in mice. The effect seems to be due to a change in function of certain immune cells which play a critical role in cancer immunity. The further exploration of this finding might be beneficial for improving anti-cancer immunotherapies.
Salt impacts experimental tumor models
High salt intake is a known risk factor for high blood pressure and cardiovascular diseases. Recent research has also indicated that too much salt may impact autoimmunity. Studies have shown that a high salt diet could change the immune cell balance towards a more aggressive state and worsen autoimmunity. Interestingly, these shifts in the immune cell balance, though detrimental in autoimmune conditions, could be in theory useful in anti-cancer immune therapies to improve immune attacks against tumor cells.
An international research team led by Prof. Kleinewietfeld that included Prof. Sven Brandau (University of Duisburg-Essen, Germany), Dr. Thomas Kammertöns (Charite & MDC-Berlin, Germany) and Prof. Jo Van Ginderachter (VIB-VUB) have now investigated the impact of high salt intake on tumor growth in mice. They found that a high salt diet inhibited tumor growth in two independent mouse models. The research team further found 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.
Immune cells changing function
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. Moreover, if these cells were depleted, the effect of a high salt diet on tumor growth in mice was undone.
MDSCs are suspected to be an important mechanism that prevents an efficient immune attack against tumors in anti-cancer 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.
Prof. Kleinewietfeld (VIB-UHasselt): "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. However, future studies are needed to fully understand the effect and the detailed underlying molecular mechanisms behind to judge its therapeutic potential for anti-cancer immunotherapies.
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Publication
High salt inhibits tumor growth by enhancing anti-tumor immunity, Willebrand et al., Frontiers in Immunology.
DOI: 10.3389/fimmu.2019.01141
Funding
MKL was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (640116), by a SALK-grant from the government of Flanders, Belgium and 1541 by an Odysseus-grant of the Research Foundation Flanders 1542 (FWO), Belgium.
Questions from patients
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Journal
Frontiers in Immunology