The ingestion of excess salt could proffer antitumor effects, according to the results of a preclinical study published in Frontiers in Immunology.
Although the consumption of excess salt is widespread in Western diets and has been linked to pro-inflammatory effects in cardiovascular, metabolic, and autoimmune diseases—such as multiple sclerosis and inflammatory bowel disease—it may be of beneficial use in the fight against cancer.
In the current study, high salt intake stymied tumor growth in two mouse transplantation models. One of the models was of lung cancer and the other was of melanoma.
Mice fed a high-salt diet exhibited delayed tumor outgrowth by day 11 post-injection of B16-F10 melanoma cells. By day 13 post-injection, there were significant differences in tumor size in mice in the high-salt diet group vs those in the control diet group. This effect extended to when the mice were killed on days 15-17 post-injection.
The antitumor effect seemed to be independent of adaptive immune cells, such as T cells, and rather due to functional modulation of myeloid-derived suppressor cells (MDSCs).
Using cell cultures, the researchers found that excessive salt consumption inhibited the function of MDSCs, a cell type that has been shown, in previous studies, to prevent the immune system from fighting tumors. MDSCs are a diverse population of immature myeloid cells, which don’t terminally differentiate, and employ a strong immune suppression in mice and humans.
The consumption of excess salt could change the immune-cell balance in favor of a pro-inflammatory state, which is hypothesized to be beneficial in terms of anti-cancer immunity.
MDSC induction from myeloid progenitors happens in the bone marrow and spleen—usually in the setting of chronic inflammation. This induction results in the accumulation of MDSCs in cancer, where they can inhibit different immune cells—including T and B cells, dendritic cells, and natural killer cells—thus playing a role in the immune suppressive states via different molecular mechanisms.
The authors suggested that molecular changes triggered by high salt conditions could present novel immunotherapeutic targets. Of note, MDSCs are thought to be substantial hurdles in cancer immunotherapy, given that they prevent efficient immune attack against tumors—such as when using checkpoint inhibitors—and could potentially be targeted by salt.
“We show that a high-salt diet significantly delays tumor growth in two independent murine tumor transplantation models,” concluded the authors. “This effect seems to be mediated through enhanced anti-tumor immunity by a functional inactivation of MDSCs. Since high salt conditions also affected human MDSCs in a similar manner, our data suggest that the targeting of this mechanism could potentially be a novel beneficial strategy to block MDSC function in settings of cancer immunotherapy.”