Fasting reprograms the immune system

A team of researchers has shown for the first time that fasting can reprogram the metabolism of natural killer cells, helping them survive the harsh conditions in and around tumors while improving their ability to fight cancer.

Fasting remodels specific tissue niches to enhance NK cell-mediated antitumor immunity.

Summary

Fasting is associated with better cancer outcomes. Here, we examined the effects of fasting on natural killer (NK) cell antitumor immunity. Cyclic fasting increased immunity against solid and metastatic tumors in an NK cell-dependent manner. During fasting, NK cells redistributed from peripheral tissues to the bone marrow (BM). In humans, fasting also reduces the number of circulating NK cells. NK cells in the spleen of fasted mice were metabolically remodeled by increased concentrations of fatty acids and glucocorticoids, increasing fatty acid metabolism through increased expression of the CPT1A enzyme, and Cpt1a knockdown affected NK cell survival and function in this environment. In parallel, the redistribution of NK cells into the BM during fasting required the trafficking mediators S1PR5 and CXCR4. These cells were treated with a large pool of BM myeloid cells expressing interleukin (IL)-12, which enhanced IFN-γ production. Our findings identify a link between dietary restrictions and optimized innate immune responses, which could potentially improve immunotherapy strategies.

Comments

Periods of fasting reprogram the immune system’s natural killer cells to better fight cancer, according to a new study in mice led by researchers at Memorial Sloan Kettering Cancer Center (MSK).

Fasting and other dietary regimens are increasingly being researched as ways to deprive cancer cells of the nutrients they need to grow and make cancer treatment more effective.

Now, a team of researchers from the MSK Sloan Kettering Institute and their colleagues have shown for the first time that fasting can reprogram the metabolism of natural killer cells, helping them survive the harsh conditions in and around tumors, while also improving your ability to fight cancer. . ability. The study, led by postdoctoral researcher Rebecca Delconte, Ph.D., was published in the journal Immunity.

The findings may help explain one mechanism by which fasting may help the body protect against cancer, as well as reduce overall fat and improve metabolism. And while more research is needed, the results also suggest that fasting may be a strategy for improving immune responses and increasing the effectiveness of immunotherapy, the study authors noted.

“Tumors are very hungry”says immunologist Joseph Sun, PhD, lead author of the study. “They absorb essential nutrients, creating a hostile environment, often rich in lipids that are harmful to most immune cells. Here we show that fasting reprograms these natural killer cells to better survive 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 first encountering it, unlike T cells, which require prior exposure to a specific enemy to trigger a specific response.