Salt the tumor
Salt as a modulator of immunity in cancer – so far in mice
One of the common tips about a healthy diet is to eat less salt. Indeed, a diet with a high content of "white poison", as salt is often called, contributes to the development of not only hypertension, but also inflammatory processes. However, it has recently been shown that in the case of cancer, the latter effect may be useful – at least for mice.
The article by Rizvi et al High-salt diet mediates interplay between NK cells and gut microbiota to induce potential tumor immunity is published in the journal Science Advances.
It is known that with a high content in food, salt (sodium chloride, NaCl) acts as a powerful immunomodulator, causing or aggravating (in some autoimmune diseases) inflammatory reactions of the body. But is it possible to use this property of salt for the benefit of cancer patients?
A cancerous tumor has not only a local, but also a powerful systemic effect on the body. In particular, it causes a drop in blood glucose levels and electrolyte imbalance, including a decrease in blood sodium levels.
The assumption that Na+ and K+ ions affect the growth of cancer cells was first made almost a hundred years ago – back in 1933. But only in recent years, laboratory "mouse models" of cancer have shown that a diet containing a large amount of salt reduces tumor growth. But the mechanisms of this phenomenon have so far been practically unexplored.
To fill this gap, scientists from India implanted melanoma cells in laboratory mice – a malignant skin formation that developed into tumors. One group of such mice received food with the usual (0.9%) salt content, ND, the other – 1% higher than normal and the third group – high-salt (4% higher than normal, HSD).
In the first two groups, the level of Na+ ions in the blood was more than a third lower compared to healthy animals. And in the third group, who received a high-salt diet, the sodium level was restored to normal. The growth of tumors was also suppressed in these mice, which also produced fewer metastases, and the survival rate was higher.
It turned out that mice that ate a lot of salt had more active natural killer cells (NK cells) - lymphocytes that are able to recognize and destroy tumor cells, the first innate line of defense of the body. Usually, with the development of cancerous tumors, the activity of these immune cells is suppressed, but a high-salt diet in this case had a protective effect.
However, the experimenters did not stop there.
As you know, there are special receptors on lymphocytes (PD-1) that are activated when they "meet" with tumor antigens – it is these immune cells that begin to destroy a cancerous tumor. But the tumor knows how to defend itself: it produces molecules that bind to PD-1 and thus stop the proliferation of killer lymphocytes.
Therefore, in one of the variants of cancer immunotherapy, patients are injected with antibodies to PD-1, which protect immune cells from the effects of the tumor. It turned out that if such therapy in mice is combined with a high-salt diet, then the rate of melanoma growth in them is suppressed by 10 times!
By the way, in humans, anti-PD1 immunotherapy is ineffective in many cases. One of the markers of success is the high content of the hippurate compound in the blood. Its level was higher in mice on a high-salt diet. And in the feces of these animals, an increased number of bifidobacteria were found, which contribute to more effective immunotherapy of cancer in laboratory animals and humans. Previously, it was shown that hippurate is one of the byproducts of an important metabolic pathway in these bacteria.
To clarify and confirm the discovered pattern: "high–salt diet – bifidobacteria – hippurate - killer lymphocytes (NK cells) - tumor suppression", the researchers conducted several more experiments, affecting some links of this chain.
In particular, with the help of antibiotics, they "cut down" the intestinal microflora in a group of mice on a high-salt diet, and salt ceased to have a protective anti-cancer effect. However, this effect was restored after transplantation of fecal material from individuals who were not given antibiotics.
The mechanism turned out to be simple. A high-salt diet increases the permeability of the intestinal wall, and bifidobacteria were able to move from the intestines of mice directly to the sites of tumors.
This conclusion was confirmed by the experimental introduction of bifidobacteria directly into the tumor, as a result of which the level of hippurate stimulating immune cells increased in it.
By the way, tests conducted a few years ago showed that the introduction of certain bacteria directly into the tumor allows it to be reduced or even completely destroyed.
Thus, the basis for increasing antitumor immunity in the case of a high-salt diet is the interaction between bifidobacteria, as an important part of the intestinal microflora, and NK cells. In practice, this means that salt, at least, can enhance the effect of cancer immunotherapy, and, quite possibly, not only in mice, but also in humans.
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