Trans-vaccine acid (ATV), a nutrient present in beef, lamb and dairy, may help increase the capacity of therapies to remove malignant cells, according to a study published in Nature. By promoting the cytotoxic function of CD8+ T lymphocytes and tumor infiltration, ATV may enhance the clinical effects of immune checkpoint inhibitors, TCEs (T-cell engagers) and CAR-T cell therapies.
These results could form the basis of new dietary strategies to amplify the effects of therapies in oncology. Excessive consumption of red meat, however, although it may increase the levels of ATV in the blood, is associated with the risk of cancer. For this reason, new methods of using ATV as a dietary supplement must be developed.
Only a few hundred metabolites derived from food end up circulating in the blood, suggesting that they are of high importance to human biology. For this reason, investigating and describing the physiological and pathological processes in which food-derived metabolites are involved could reveal new methods to prevent and treat diseases.
ATV is the most abundant long-chain fatty acid present in milk. It cannot be synthesized in the human body. Of the intake of trans-vaccenic acid, 20% is cleaved into other compounds, and 80% remains circulating ATV.
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The study evaluated 235 nutrients present in the blood to detect those compounds that could influence antitumor immunity. Tests were performed on tumor cells and murine models, representing various types of cancer. After confirming the impact of ATV on CD8+ T lymphocyte function, the effect of increasing dietary ATV content on laboratory models of cancer was investigated.
The ATV-rich diet significantly reduced the tumor growth potential of malignant melanoma and colon cancer cells. A series of molecular and genetic analyzes were carried out, through which it was found that ATV inactivates a surface receptor – GPR43, which is activated by short-chain fatty acids, which can be produced by the intestinal microbiota. The effect of ATV is dominant compared to that of these compounds, causing the activation of the CREB cell signaling pathway, involved in cell growth, survival and differentiation.
By testing on leukemic cell lines, the addition of ATV was found to increase activity in vitro blinatumomab to eliminate these cells. In a later step, blood samples were collected from patients who received CAR-T therapy for lymphoma. It found that the level of ATV was higher in people in whom the CAR-T therapy worked, compared to those in whom it did not.
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2024-01-07 12:53:31
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