Dr. Joseph Sun, an investigator at MSK’s Sloan Kettering Institute, and postdoctoral fellow Dr. Rebecca Delconte led a laboratory study to investigate how fasting changes the immune response against cancer.
More than a dozen types of cancer are sensitive to obesity, which can cause inflammation that damages cells, increased hormone levels, and other changes. So it makes sense for researchers to explore whether fasting to lower body fat and improve metabolism might improve outcomes in cancer.
Now laboratory researchers at Memorial Sloan Kettering Cancer Center (MSK) and their collaborators have found another potential benefit to fasting: supercharging the immune system’s “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.)
Fasting can reprogram the metabolism of natural killer cells, the team found in a study of mice. Those reprogrammed cells are better able to survive in the harsh environment in and around tumors. Their cancer-fighting ability is stronger, too.
The research, which was published in Immunity — one of the top immunology journals — explains how natural killer cells get reprogrammed during periods of fasting. The researchers are optimistic that what they’re learning in animal models could one day help make immunotherapies more effective in people.
“Tumors are very hungry,” says immunologist Joseph Sun, PhD, the study’s senior author. “They use up essential nutrients, resulting in a hostile, nutrient-starved environment that is 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 get their name because they can destroy a threat without having encountered it before — unlike other immune cells, called T cells, which require prior exposure to a specific threat in order to target it.
In general, the more NK cells that are present within a tumor, the better the prognosis is for the patient.
How Fasting Reprograms NK Cells
This colorized image from a scanning electron microscope shows two human natural killer cells (yellow) attacking a cancer cell (pink). Credit: Eye of Science / Science Source
For the study, mice with cancer were denied food for 24 hours twice a week and then allowed to eat freely in between fasts. While the mice did not lose weight, the fasting had a profound effect on their natural killer immune cells.
Just as happens in humans, fasted mice saw a drop in their glucose levels and a rise in free fatty acids, which are lipids released by fat cells.
“During each of these fasting cycles, NK cells learned to use these fatty acids as an alternative fuel source to glucose,” says study first author Rebecca Delconte, PhD, a postdoctoral fellow in the Sun Lab. “This really improves their response against cancer and helps them survive in the harsh environment around the tumor.”
Fasting also led NK cells to travel to and interact with different parts of the body in an intriguing way, the researchers observed.
Many of the NK cells travel into the bone marrow, where they are reprogrammed to develop a more powerful response against cancer. Meanwhile, NK cells that travel to the spleen undergo a separate reprogramming, making them better able to use lipids as a fuel source.
“With both of these mechanisms put together, we find that NK cells within the tumor are pre-primed to better rally the immune system,” Dr. Delconte says. “They’re more able to survive in the tumor environment and their power is strengthened against cancer cells.”
Potential To Improve Cancer Treatments
There are several potential opportunities to advance the mouse-model research toward treating patients in the clinic, the researchers say.
First, clinical trials are already beginning to study the safety and effectiveness of fasting in combination with standard existing treatments. Another avenue would be to identify drugs that could target the underlying mechanisms — without requiring patients to fast. Third, NK cells might be able to be put into a fasted state outside of the body and then be administered back to patients to improve treatment effects.
Right now, however, more clinical data is still needed about the effects of fasting for people with cancer, MSK experts say.
There are many different types of fasting, and some might be helpful while others might be harmful. Patients should speak with their doctors about what’s safe and healthy for their individual situation.