Periods of fasting reprogram the immune system’s natural killer cells to better fight cancer, according to a new study in mice by researchers at Memorial Sloan Kettering Cancer Center (MSK).
Fasting and other dietary regimens are increasingly being explored as ways to deprive cancer cells of the nutrients they need to grow and make cancer treatments more effective.
Now, a team of researchers at MSK’s Sloan Kettering Institute and their collaborators have shown for the first time that fasting can reprogram the metabolism of natural killer cells, helping them survive the harsh environment in and around tumors, while also improves your ability to fight cancer. ability. The study, led by postdoctoral fellow Rebecca Delconte, PhD, was published June 14 in Immunity.
The findings could help explain one of the mechanisms by which fasting can help the body defend against cancer, in addition to reducing overall fat and improving metabolism. And although more research is needed, the results also suggest that fasting could be a strategy to improve immune responses and make immunotherapy more effective, the study authors note.
“Tumors are very hungry,” says immunologist Joseph Sun, PhD, senior author of the study. “They take up essential nutrients, creating a hostile environment often rich in lipids that are harmful to most immune cells. What we show here is that fasting reprograms these natural killer cells to better survive in this suppressive environment.”
What are natural killer cells?
Natural killer cells, or NK cells for short, are a type of white blood cell that can kill abnormal or damaged cells, such as cancer cells or cells infected with a virus. They get their name because they can destroy a threat without having encountered it first, unlike T cells, which require prior exposure to a specific enemy to mount a specific response.
In general, the more NK cells that are present within a tumor, the better the prognosis for the patient.
For the study, mice with cancer were denied food for 24 hours twice a week and then allowed to eat freely between fasts. This approach prevented the mice from losing weight overall, the authors note.
But these periods of fasting had a profound effect on NK cells.
Just as in humans, the mice saw a drop in their glucose levels and an increase in free fatty acids, which are lipids released by fat cells that can serve as an alternative energy source when no other nutrients are present. says Dr. Delconte. .
“During each of these fasting cycles, the NK cells learned to use these fatty acids as an alternative fuel source to glucose,” he says. “This really optimizes their anticancer response because the tumor microenvironment contains a high concentration of lipids, and now they can enter the tumor and survive better thanks to this metabolic training.”
Fasting reprograms NK cells
The researchers noted that fasting also led to a redistribution of NK cells within the body.
Many of the NK cells traveled to the bone marrow, where, thanks to fasting, they were exposed to high levels of a key signaling protein called interleukin-12. This primed the NK cells to produce more interferon gamma, a cytokine that plays an important role in anti-tumor responses.
Meanwhile, NK cells in the spleen were undergoing separate reprogramming, making them better at using lipids as a fuel source.
“With both mechanisms together, we found that NK cells are pre-primed to produce more cytokines within the tumor,” says Dr. Delconte. “And with metabolic reprogramming, they are better able to survive in the tumor environment and become specialized to have enhanced anti-cancer properties.”
It’s not yet clear whether there are two separate populations of NK cells that are trained differently in different parts of the body, or whether the cells end up passing through both sites during their week-long life cycle.
“That’s the million-dollar question,” says Dr. Sun. “And one that we have only begun to answer using the cell labeling techniques we used in this study.”
While no human bone marrow samples were studied as part of the project, the researchers note that blood samples from cancer patients show that fasting causes a reduction in freely circulating NK cells in people, as they observed in mice.
Potential to improve cancer treatments
According to the researchers, there are several potential opportunities to advance mouse model research toward the clinic. First, clinical trials are already beginning to study the safety and effectiveness of fasting in combination with existing standard treatments. Another avenue would be to identify drugs that could target the underlying mechanisms without requiring patients to fast. Third, NK cells could be fasted outside the body and then administered to enhance the effects of the treatment.
However, more clinical data are currently still needed on the effects of fasting in people with cancer, says Neil Iyengar, MD, a breast medical oncologist at MSK and a leading researcher on diet, metabolism and cancer, who was not directly involved in the study. the study. study.
“There are many different types of fasting, and some can be helpful while others can be harmful,” he says. “Patients should talk to their doctors about what is safe and healthy for their individual situation.”