Fasting supercharges the cancer-killing properties of immune cells

Things that help the body fight cancer are good, especially if they’re easy to implement and don’t require a doctor’s prescription. In a recent study, researchers from the Memorial Sloan Kettering (MSK) Cancer Center in New York investigated how fasting boosts the immune system’s cancer-fighting abilities.

“Tumors are very hungry,” said Joseph Sun, an immunologist and the study’s co-corresponding author. “They take up essential nutrients, creating a hostile environment often rich in lipids that are detrimental to most immune cells. What we show here is that fasting reprograms these natural killer cells to better survive in this suppressive environment.”

Natural killer (NK) cells are white blood cells that live up to their name, destroying other cells infected with viruses and cancer cells. Although their primary job is to kill invaders, NK cells also communicate with other immune cells, releasing proteins called cytokines to signal them to attack harmful cells. The more NK cells there are invading a cancer tumor, the better the patient’s prognosis.

The researchers fasted mice with cancer for 24 hours twice a week; they could eat freely between fasts. They found that fasting had a profound effect on the animal’s NK cells. As happens in humans who fast, the mice’s glucose levels fell, and free fatty acids, which can be used as an alternative energy source when other nutrients are low, rose. NK cells in the mice’s spleen were ‘reprogrammed’ as a result.

“During each of these fasting cycles, NK cells learned to use these fatty acids as an alternative fuel source to glucose,” said the study’s lead author, Rebecca Delconte. “This really optimizes their anti-cancer response because the tumor microenvironment contains a high concentration of lipids, and now they’re able to enter the tumor and survive better because of this metabolic training.”

In addition to providing an alternative energy source, fasting also caused NK cells to relocate. Many moved into the bone marrow where, because of fasting, they were exposed to high levels of a signaling protein called Interleukin 12. This boosted the cells’ production of Interferon-gamma, one of the anti-tumor cytokines they make naturally.

“With both of these mechanisms put together, we find that NK cells are pre-primed to produce more cytokines within the tumor,” Delconte said. “And with the metabolic reprogramming, they’re more able to survive in the tumor environment, and specialized to have improved anti-cancer properties.”

The researchers are now investigating whether there are two populations of NK cells that receive different training in either the spleen or the bone marrow or whether all cells pass through both sites.

The present study adds to existing evidence showing that fasting can be used as an adjunct to chemotherapy treatment for cancer. In addition, the study may lead to the identification of drugs that target the mechanisms caused by fasting without requiring patients to fast. Another alternative would be to collect NK cells in a fasted state and keep them outside the body, later administering them as a supplementary treatment.

Until there’s further research into the effects of fasting on cancer in humans, doctors are urging people to speak with their doctors before they fast.

“There are many different types of fasting, and some might be helpful, while others might be harmful,” said Neil Iyengar, a breast cancer specialist at MSK who was not involved in the study. “Patients should speak with their doctors about what’s safe and healthy for their individual situation.”

The study was published in the journal Immunity.

Source: MSK Cancer Center

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