Nutrient Spotlight: Investigating the Role of Trans-Vaccenic Acid in Anti-Tumor Immunity
A recent study conducted by researchers at the University of Chicago investigates the impact of trans-vaccenic acid (TVA), a long-chain fatty acid found in meat and dairy products, on the immune system’s ability to combat cancer. This nutrient, prevalent in grazing animals like cows and sheep, shows potential in improving the functions of CD8+ T cells, a vital component of the immune system responsible for infiltrating tumors and attacking cancer.
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Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
Nutrients play a crucial role in human physiology, providing both energy and essential building blocks while also acting as regulatory molecules. Despite this integral connection, the precise mechanisms through which circulating nutrients impact specific physiological processes in the human body remain largely elusive. To address this, we employed a screening approach based on a blood nutrient compound library.
Our research demonstrates that trans-vaccenic acid (TVA), a dietary component, directly enhances the function of effector CD8+ T cells and boosts anti-tumor immunity in vivo. TVA is the primary form of trans-fatty acids found in human milk, yet the human body cannot produce it internally. Circulating TVA primarily comes from ruminant-derived foods like beef, lamb, and dairy products such as milk and butter. Notably, only a fraction of dietary TVA is converted to rumenic acid by humans or mice.
Mechanistically, TVA deactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by short-chain fatty acid ligands. By antagonizing the short-chain fatty acid agonists of GPR43, TVA activates the cAMP–PKA–CREB axis, thereby enhancing CD8+ T cell function. These findings unveil TVA derived from the diet as a mechanism for externally reprogramming CD8+ T cells, distinct from the short-chain fatty acids derived from the gut microbiota. This highlights the translational potential of TVA for treating tumors.
FOR MORE INFORMATION:Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
RESEARCH METHODLOGY
Led by DR .CHEN and collaborators, the study involves a comprehensive exploration of TVA’s effects on anti-tumor immunity. To identify its influence, researchers utilized a “blood nutrient” compound library, comprising 255 bioactive molecules derived from nutrients. The screening process targeted the activation of CD8+ T cells critical for immune responses against cancer.
Dr. Chen is keen on unraveling the intricate connections between metabolic and cell signaling networks to gain deeper insights into cancer metabolism, ultimately aiming for improved clinical outcomes.
The primary research objectives encompass :
1. Exploring the metabolic and signaling roles of intracellular metabolites and circulating “blood chemicals” that impact tumorigenesis, tumor progression, and responses to anti-cancer therapies such as chemotherapy and immunotherapy
2 .Understanding the mechanistic basis linking diets and specific oncogenic mutations. This involves investigating the pro- and anti-tumor effects of diet-derived substances on tumors with distinct genetic backgrounds.
Standout Performer: Among the screened compounds, TVA emerged as the most promising, demonstrating its effectiveness in enhancing anti-tumor immunity.
Molecular Insights: Through molecular and genetic analyses, employing innovative techniques like KAS-seq, researchers uncovered how TVA influences T cells. Notably, TVA was found to deactivate the GPR43 receptor on cell surfaces, initiating the CREB pathway crucial for cellular growth, survival, and differentiation.
Inhibiting Tumor Growth: In mouse models fed a diet enriched with TVA, there was a significant reduction in tumor growth, particularly observed in melanoma and colon cancer cells. This study underscores the potential role of TVA in hindering tumor development.
Clinical Significance: Analysis of blood samples from patients undergoing CAR-T cell immunotherapy revealed that those with higher TVA levels responded more favorably. TVA also heightened the effectiveness of an immunotherapy drug against leukemia cells.
Dietary Supplement Prospects: While stressing the need to determine the optimal TVA dosage, researchers propose TVA as a potential dietary supplement for T cell-based cancer treatments
ReAD MORE SCIENTIFIC RESEARCHED article:B and T Cells Unveiled, The Maestros Behind Healthy Immune System Harmony
FUTURE DIRECTION
The study underscores the importance of a “metabolomic” approach to unraveling how dietary components, such as TVA, influence health. The researchers aspire to build an extensive library of circulating nutrients to comprehend their broader impact on immunity and various biological processes, including aging.
CONCLUSION
In the complex interplay between diet and immunity, the study illuminates TVA’s targeted mechanism on CD8+ T cells, offering insights into its profound physiological responses at the organism level. This research paves the way for further investigations into similar nutrients, possibly derived from plant sources, and their potential contributions to immune function.
