Williams Cancer Institute

TVA: A DIETARY ALLY AGAINST TUMORS

TVA: A DIETARY ALLY AGAINST TUMORS


Dietary nutritional availability emerges as a crucial element in the environmental influences that have shaped human physiology over millions of years of evolution.

Despite extensive studies on the connection between diet and human health, there is a knowledge gap regarding how circulating diet-derived nutrients affect specific physiological and pathological processes.

In a study conducted by Fan et al. in 2023, using a genomic screening approach based on a library of 633 blood nutritional compounds, it was particularly found that trans-vaccenic acid (TVA) plays an immunomodulatory role in directly promoting the function of effector CD8+ T cells and in vivo antitumor immunity.

The findings reveal that TVA activates the function of CD8+ T cells by inactivating the cell-surface receptor GPR43.

This receptor is modulated by short-chain fatty acid ligands, and TVA acts as an antagonist to these ligands, resulting in the activation of the cAMP-PKA-CREB axis to enhance CD8+ T cell function.

Although TVA is the predominant form of trans-fatty acids in breast milk, the human body cannot produce it internally.

Nevertheless, TVA is naturally present in ruminant-derived foods such as beef, lamb, and dairy products.

This suggests that diet-derived TVA represents a mechanism for extrinsic reprogramming of CD8+ T cells, with translational potential in tumor treatment.

However, further studies are needed to elucidate the underlying structural and molecular mechanisms by which TVA inactivates GPR43.

Reference: Hao Fan, Siyuan Xia, Junhong Xiang, Yuancheng Li, Matthew O. Ross, Seon Ah Lim, Fan Yang, Jiayi Tu, Lishi Xie, Urszula Dougherty, Freya Q. Zhang, Zhong Zheng, Rukang Zhang, Rong Wu, Lei Dong, Rui Su, Xiufen Chen, Thomas Althaus, Peter A. Riedell, Patrick B. Jonker, Alexander Muir, Gregory B. Lesinski, Sarwish Rafiq, Madhav V. Dhodapkar, Wendy Stock, Olatoyosi Odenike, Anand A. Patel, Joseph Opferman, Takemasa Tsuji, Junko Matsuzaki, Hardik Shah, Brandon Faubert, Shannon E. Elf, Brian Layden, B. Marc Bissonnette, Yu-Ying He, Justin Kline, Hui Mao, Kunle Odunsi, Xue Gao, Hongbo Chi, Chuan He & Jing Chen, 22 November 2023, Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity, https://www.nature.com/articles/s41586-023-06749-3

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