In medicine, sometimes the bad guys aren’t so bad and the good guys aren’t so good. Often it has to do with the quantities, the timing or even the ability to separate the wheat from the chaff. For example, chemotherapy, one of the most effective cancer treatments, was the byproduct of mustard gas, a biological weapon; Vitamin A, on the other hand, 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 are always important. This is once again evident from research published this week in the journal Nature, which concludes that red meat — a food that nutritionists recommend limiting as much as possible — contains a nutrient that improves the immune response against cancer. After research in animal models and human cells, the researchers concluded that trans-vaccenic acid, a trans fatty acid found in beef, milk and butter, has potential as a nutritional supplement to optimize the impact of immunotherapy in oncology. Still, experts recommend caution when interpreting the results.
A group of researchers from the University of Chicago focused on the nutrients circulating in the blood, about 700 substances, including organic metabolites, lipids and proteins, that could play a role in health and disease. “There are still many things we don’t know yet. A comprehensive understanding of the diverse physiological and pathological functions of each nutrient from different foods is still not available. Our study sought 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 assessed a sort of library of more than 200 food-derived nutrients circulating in the blood, and studied which ones might play a role or influence anti-tumor immunity. Their research found that a particular trans fat, trans-vaccenic 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, so TVA is not a typical nutrient for energy or as a biosynthetic building block for macromolecules. Our research shows that TVA has regulatory functions,” said Chen.
The 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 animals fed a control diet. The study also found that a TVA-enriched diet helps CD8+ T cells better infiltrate tumors. “Our studies in mouse models demonstrate the antitumor activity of TVA through the improvement of CD8+ T cell function. This warrants future clinical trials using TVA as an adjunct to treatment with T cell-based immunotherapies,” Chen explains.
The scientists also tested what happened when some treatments were combined with this nutrient, and found that dietary TVA, added to a form of immunotherapy, “showed a synergistic attenuation of tumor growth.” In another retrospective clinical study, the authors noted that patients with lymphoma and higher TVA levels 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 can recognize and identify these better. kill cancer cells and then reinject them into their bodies. “These findings are consistent with the idea that dietary TVA may improve clinical response to T cell-based immunotherapies,” the researchers suggest.
According to the authors, this study opens the door for further investigation into the possible role of circulating nutrients in human health and disease. In the case of TVA, they add, there are epidemiological studies suggesting that circulating levels of this trans fatty acid in humans are associated with lower lipid levels, diabetes risk and systemic inflammation, although its effects on cancer and cardiovascular risk and vascular diseases are unclear. . Chen admits that they still don’t know whether this nutrient could be harmful in other contexts or for other ailments, but emphasizes: “TVA is not a bad trans fatty acid, as 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.”
Focus 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 therapy responses is crucial for dietary choices. “Consuming red meat may provide TVA for improved antitumor immunity, but high red meat intake is positively associated with the risk of many cancers, including breast, colorectal, colon, and rectal cancer,” they write. In fact, the authors clarify that what their studies support is “TVA supplementation as a more targeted and efficient way than dietary changes to promote antitumor immunity.”
“Our results suggest that a balanced diet is likely to be good for your health. It may be more important to focus on the bioactivity of nutrients rather than individual foods, and taking supplements with fortified bioactive nutrients is likely more efficient than consuming foods containing these nutrients,” says Chen. The scientist assures that TVA “as a natural food component has a high translational potential as a nutritional 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 for treating cancer patients. TVA can be combined with specific T cell activators such as [the drug] blinatumomab, to treat patients with B-cell acute lymphocytic leukemia, or with CAR T cells to improve efficacy in treating cancer patients.”
Miguel Quintela, director of the Clinical Research Program of the Spanish National Cancer Research Center (CNIO) and head of a spin-off of personalized oncology nutrition (TCNterapia), warns that although this study is “a very important first observation”, it is still too early to make recommendations. “I cannot advise my cancer patients to eat a steak. An experimental demonstration is one thing, but it is another to see in the long term whether a disease is actually increasing or decreasing.” The oncologist admits that the results of the study, 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 eat nothing but that. Each nutrient occurs in foods with a complex composition. The end consumer cannot isolate that nutrient from the meat. Yet this study opens up more areas of study.”
What this research does mean, according to Quintela, is an impetus for precision nutrition. “We have to be much more precise,” he says. “[TVA] is a saturated fatty acid, which nutritionists tell us not to eat, and it in itself has lipid-lowering, anti-inflammatory, antidiabetogenic and antitumor properties, promoting the antitumor immune response. In other words: it is a trans fatty acid that is beneficial to health.” The oncologist adds a final consideration: “Ultimately, food consists of hundreds of different molecules. Overall, the effect of red meat is probably poor, as shown by many epidemiological studies. But that doesn’t mean it doesn’t contain specific nutrients that perform positive functions. Hence the need to take a precise approach that goes beyond the generalizations you hear everywhere.”
Above all, caution
Antoni Agudo, head of the Nutrition and Cancer Unit at the Catalan Institute of Oncology, thinks the study, in which he did not participate, is “very well documented” but calls for “caution” in interpreting the results. “TVA appears to have a fairly specific effect, namely reprogramming CD8+ T cells to activate immunity. But the immune system has many mechanisms of action and this is just one of them. This means it may have potential in some types of tumors or in people on specific treatments, but not in all cases of cancer.”
Furthermore, Agudo emphasizes that these findings are described “in animal experimental models and in human cells in vitro.” “There is still a long way to go between the effects observed in animals and the moment when, if ever, they will have an impact in clinical practice.”
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