Scientists at the Van Andel Research Institute found that reducing caloric intake can help immune cells fight cancer. Consequently, physicians and researchers are hoping to develop a dietary plan to boost the immune system and enhance cancer immunotherapy for patients.
A growing topic in the field of cancer research includes diet as a form of complimentary therapy. Many researchers are investigating specific nutrients to reduce risk of cancer as well as improve cancer treatment. More reports are stating that dietary restriction has anti-tumor benefits; however, it is unclear how this works biologically. A recently published article in Nature Metabolism, by Dr Russell Jones and others, demonstrate how dietary restriction provides the proper nutrients to immune cells, which improve their activity. Jones is the Chair and Professor of the Department of Metabolism and Nutritional Programming at the Van Andel Research Institute. His work focuses on immunometabolism, tumor immunology, metabolomics, and diet-genetic interactions in immunology and cancer. Jones’ research has recently focused more on how diet restriction reshapes immune cell metabolism.
Dietary restriction is the process of reducing overall caloric intake while also eating a healthy diet. Previous work from others reports that modest caloric restriction improves metabolic function, as well as delay age-related diseases. However, too much caloric restriction can have deleterious effects and cause nutrient deficiency, muscle loss, low blood-sugar, and depression.
Researchers used mouse models and metabolomic analyses to investigate the underlying biological mechanisms that improve immune cell function. Mice were given low-fat, high-protein meals once a day with ~50% fewer calories than other mice. As a result, the lower caloric intake developed ketones that fueled and generated more robust immune cells. Specifically, these immune cells were reprogrammed and more likely to identify and target cancer cells, compared to the immune cells in mice that received a “normal” caloric diet. Ketones were also found to prevent immune exhaustion, which is an inactive state due to overstimulation. Ketones are metabolic by-products that are produced when glucose levels decrease. Ketone levels are also increased during exercise or fasting. It is a compensatory output to nutrient deprivation.
Previous work by Jones and his team discovered that immune cells prefer ketones to glucose because ketones allow immune cells to better adapt to foreign pathogens. Scientists suspect that immune cell adaptation to various nutrients is an evolutionary trait in response to a time when resources were scarce. Interestingly, cancer cells can also use ketones to fuel growth. Consequently, scientists were puzzled on how to deliver ketones to immune cells and restrict this nutrient to tumor cells. While scientists are still trying to understand this phenomenon, Jones and others emphasize that caloric restriction improves immune cell antitumor activity and outweighs the off-target effect of ketones also fueling cancer cells. However, caloric restriction is not a solution to prevent or treat cancer. Scientists advise diet to only compliment therapies and improve quality of life in patients. The next steps include investigating diet strategies to enhance immunotherapy treatments. Scientists hope these findings can help develop dietary guidelines for patients with cancer. Overall, this work helps more clearly define how immune cells improve antitumor activity and provides insight into how diet can affect therapeutic outcomes.
Van Andel Research Institute, article, Nature Metabolism, Russell Jones