by In medicine, sometimes the bad guys aren’t so bad and the good guys aren’t so good. It often has to do with quantities, timing, or even the ability to separate the wheat from the chaff. Chemotherapy, for example, one of the most effective cancer treatments, was the byproduct of mustard gas, which is a biological weapon; Vitamin A, for its part, is an essential substance for the formation and maintenance of soft tissues and bones and has antioxidant properties, but in excess it can cause skin problems, bone weakness and joint pain.
Nuances always matter. This is demonstrated once again by research published this week in the journal Nature, which concludes that red meat – a food that nutrition experts recommend limiting as much as possible – contains a nutrient that improves the immune response against cancer. After conducting studies with animal models and human cells, researchers concluded that transvaccenic acid, a trans fatty acid found in beef, milk and butter, has potential as a dietary supplement to optimize Impact of immunotherapy in oncology. Still, experts recommend caution when interpreting the results.
A group of researchers at the University of Chicago focused on nutrients circulating in the blood—approximately 700 substances, including organic metabolites, lipids, and proteins—that could play a role in health and disease. “There are still many things we still don’t know. A comprehensive understanding of the various physiological and pathological functions of each nutrient in different foods is not yet available. “Our study attempted to address this dilemma,” said study author Jing Chen, professor in the Department of Medicine and director of the Cancer Metabolomics Research Center at the University of Chicago.
The scientists reviewed a library of more than 200 dietary-derived nutrients circulating in the blood and studied which ones could play a role or influence anti-tumor immunity. Their research revealed that a particular trans fat, transvaccenic acid (TVA), promoted the ability of a type of immune system cell (CD8+ T cells) to infiltrate tumors and kill malignant cells. “Only about 19% or 12% of dietary TVA can be converted to rumenic acid by humans or mice, respectively, so TVA is not a typical nutrient for energy or as a biosynthetic component of macromolecules. Our study shows that the TVA has regulatory functions,” says Chen.
Experiments with mice showed that a diet enriched with this trans fat reduced the expansion capacity of melanoma and colon cancer tumor cells, compared to those animals fed a control diet. The research also revealed that a TVA-enriched diet helps CD8+ T cells better infiltrate tumors. “Our studies in mouse models show the antitumor activity of TVA through improving CD8+ T cell function. This justifies future clinical studies using TVA as an adjunct to treatment with T cell-based immunotherapies,” explains Chen.
The scientists also tested what happened when some treatments were combined with this nutrient and found that dietary TVA added to a type of immunotherapy “showed synergistic attenuation of tumor growth.” In another retrospective clinical study, the authors observed that lymphoma patients who had higher levels of TVA responded better to CAR-T, another type of immunotherapy that involves extracting T lymphocytes from patients to enhance them in the laboratory so that they recognize and kill the cancer cells and then reinject them into your body. “These findings align with the idea that dietary TVA may improve clinical responsiveness to T cell-based immunotherapies,” the researchers suggest.
According to the authors, this study opens the door to further inspection of the possible roles of circulating nutrients in human health and disease. In the case of TVA, they add, there are epidemiological studies that suggest that circulating levels of this trans fatty acid in humans are associated with lower adiposity, risk of diabetes and systemic inflammation, although its effects on the risk of cancer and cardiovascular diseases are not established. clear. . Chen admits that they do not yet know if this nutrient can be harmful in other contexts or for other ailments, but insists: “TVA is not a bad trans fatty acid, because previous studies have shown that in models of dyslipidemia [abnormal levels of fats in the blood] “In rodents, the TVA-enriched diet has hypolipidemic effects by reducing circulating triglycerides.”
Focusing on the nutrient, not the food
However, Chen and his team emphasize that a comprehensive understanding of the interactive and collective influences of various dietary nutrients on cancer risk, development, and therapeutic responses is crucial for dietary choice. “Red meat consumption may provide TVA to enhance antitumor immunity, but high red meat intake has been positively associated with the risk of many cancers, including breast, colorectal, colon, and rectal cancer,” they write. The authors clarify, in fact, that what their studies support is “TVA supplementation as a more specific and efficient way than dietary changes to benefit antitumor immunity.”
“Our results suggest that a balanced diet is probably good for health. Focusing on the bioactivity of nutrients rather than individual foods may be more important, and taking supplements with enriched bioactive nutrients is likely more efficient than consuming foods containing these nutrients,” Chen says. The scientist assures that “as a natural component of food, TVA has a high translational potential as a dietary element in therapeutic approaches to improve the clinical results of various anticancer therapies.” He cites several examples: “A combination of TVA and immune checkpoint inhibitors could be tested to improve immunotherapies to treat cancer patients. TVA can be combined with specific T cell activators such as [the drug] blinatumomab, to treat patients with B-cell acute lymphoblastic leukemia, or with CAR-T cells to improve efficacy in the treatment of cancer patients.”
Miguel Quintela, director of the Clinical Research Program at the National Cancer Research Center (CNIO) and head of a personalized oncological nutrition spin-off (TCNterapia), warns that, although this study is “a very important first observation”, it is too early to start issuing recommendations. “I can’t suggest my cancer patients eat steak. “An experimental demonstration is one thing and another is to see, in the long term, if a disease really increases or decreases.” The oncologist admits that the results of the research, in which he did not participate, seem “robust”, but it is necessary to know how to interpret and contextualize them. “Right now you can’t make a list of pure nutrients and not eat anything other than that. Each nutrient occurs in foods of complex composition. The final consumer cannot isolate that nutrient from the meat. Still, this study opens up more fields of study.”
What this research does represent, in Quintela’s opinion, is a boost to precision nutrition. “We need to be much more precise,” he says. “[TVA] It is a saturated fatty acid, which nutrition experts recommend us not to eat, and by itself it has lipid-lowering, anti-inflammatory, antidiabetogenic and antitumor capabilities, favoring the antitumor immune response. In other words, it is a trans fatty acid that is beneficial for health.” The oncologist adds a final reflection: “At the end of the day, a food is made up of hundreds of different molecules. In general, the effect of red meat is probably bad, as demonstrated by numerous epidemiological studies. But that does not mean that it does not have specific nutrients that exert positive functions. Hence the need to take a precise approach, beyond the generalizations that are heard everywhere.”
Above all, caution
Antoni Agudo, head of the Nutrition and Cancer Unit of the Catalan Institute of Oncology, believes that the study, in which he did not participate, is “very well documented”, but calls for “prudence” when interpreting the results. “TVA has been shown to have a fairly specific effect, which is the reprogramming of CD8+ T cells to activate immunity. But the immune system has many pathways of action and this is just one of them. This means that it may have potential in some types of tumors or in people who are following a specific treatment, but not in all cases of cancer.”
Furthermore, Agudo emphasizes, these findings are described “in experimental animal models and in human cells in vitro.” “There is a long way from effects being seen in animals to having an impact, if ever, in clinical practice.”
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