Trans-vaccenic acid reprograms CD8⁺ T cells and anti-tumour immunity

Area of Science:

• Immunology
• Nutrition Science
• Cancer Research

Background:

• Dietary nutrients are crucial for human physiology, but their precise mechanisms influencing bodily processes are not fully understood.
• Circulating nutrients, like trans-vaccenic acid (TVA), play regulatory roles, yet their specific impacts on immune function require further elucidation.

Purpose of the Study:

• To investigate the mechanisms by which dietary nutrients, specifically trans-vaccenic acid (TVA), influence immune cell function and anti-tumour immunity.
• To identify the molecular targets and pathways through which TVA exerts its effects on CD8+ T cells.

Main Methods:

• Utilized a blood nutrient compound library-based screening approach to identify bioactive dietary compounds.
• Investigated the in vivo effects of dietary TVA on effector CD8+ T cell function and anti-tumour immunity.
• Examined the molecular mechanisms, including receptor interactions and signaling pathways (cAMP-PKA-CREB axis), involved in TVA's immunomodulatory effects.

Main Results:

• Dietary trans-vaccenic acid (TVA) was identified as a direct promoter of effector CD8+ T cell function and anti-tumour immunity in vivo.
• TVA was found to inactivate the immunomodulatory receptor GPR43 by antagonizing its short-chain fatty acid ligands.
• This inactivation leads to the activation of the cAMP-PKA-CREB signaling axis, enhancing CD8+ T cell function.

Conclusions:

• Diet-derived TVA represents a host-extrinsic mechanism for reprogramming CD8+ T cells, distinct from gut microbiota-derived short-chain fatty acids.
• TVA demonstrates significant translational potential for the development of novel cancer immunotherapies.