Salt has been used for a myriad of reasons throughout history. Not only did individuals use it to preserve food, but it was also used to garden, to construct new roads, and in religious ceremonies. Salt was even used as a form of currency. Even today we use salt to flavor food, heal a sore throat, clean metal, remove stains, and relieve bee stings, among others. Therefore, the idea to use salt as a healing method is not new. Salt or sodium chloride draws water from cells and, consequently, takes any bacteria floating in that liquid. It can clear open wounds and rid the body of lingering bacteria that could infect the patient. While salt is used for all these things, particularly wound healing, scientists are unsure of their systemic impact on immune cells. There is limited research linking immunity with salt, with the exception that large amounts of salt intake are deleterious to the body. More specifically, scientists were previously unaware of the implications table salt might have on cancer immunotherapy outcomes.
Cancer immunotherapy has rapidly progressed in the last decade. In many cases, immunotherapy is being combined with standard-of-care therapy or given as a single agent. The difference between immunotherapy and chemotherapy is that immunotherapy works to direct the immune system toward the tumor. In many cases, immunotherapy activates immune cells responsible for targeting cancer cells, such as T cells. Alternatively, chemotherapy is a chemical that targets cellular mechanisms that kill or lyse the cancer cells. Unfortunately, chemotherapy is not specific, and can lead to adverse side effects. However, combination therapies has been shown to improve longevity in patients and even result in remission.
One form of immunotherapy includes chimeric-antigen receptor (CAR) T cells. CAR-T cells are immune cells drawn from the patient and engineered to recognize the tumor. Once these cells are engineered and grown up in the lab, they are then reinfused into the patient. Unfortunately, there are still many suppressive mechanisms in the tumor microenvironment (TME) that dysregulate T cell metabolism, limiting their efficacy. However, researchers have recently discovered how sodium ions, from table salt, can improve antitumor T cell activity. The recent article in Nature Immunology, by Dr. Christinia Zielinski and others demonstrated how breast cancer cells have high sodium concentrations and that T cells respond better in a high sodium environment.
It has previously been shown that sodium regulates T cells in other disorders, but until now, it was unclear how it influenced T cells in cancer. Evidence of this phenomenon was recorded after multiple experimental designs, including work done in mice. For example, researchers treated T cells with salt and then co-cultured them with tumor cells. As a result, the T cells effectively targeted the tumor cells compared to T cells not treated with salt. Zielinski and others concluded that salt improves the metabolic fitness of T cells by increasing signal for the uptake of nutrients used for cell energy, including sugar and amino acids. More specifically, this signal amplification made it easier for cells to function properly and protected them from the TME that would normally dysregulate their activity.
Salt used to improve T cell efficacy is a paradigm-shifting discovery. This report demonstrates the impact of sodium on immune cells within the context of cancer, which was previously unknown. Although, this does not indicate patients should eat more salt, it does provide insight into generating more effective therapies, such as CAR-T cells in the clinic.