Objective:

To explore how one-carbon metabolism influences T-cell function, epigenetic modifications, and potential therapeutic strategies in cancer immunity.

Approach:

• Nutrient Competition: Examines how tumor cells deplete methionine, affecting T-cell function and leading to immune dysfunction.
• Epigenetic Programming: Discusses the role of one-carbon metabolism in regulating histone methylation and T-cell activation.
• Therapeutic Modulation: Highlights potential strategies such as methionine restriction and serine-pathway targeting to enhance antitumor immunity.

Key Findings:

• One-carbon metabolism regulates nutrient competition and T-cell functional state.
• Tumor-intrinsic one-carbon pathways promote immune escape through PD-L1 upregulation and suppression of innate immune sensing.
• Therapeutic modulation of one-carbon metabolism may enhance responses to immune checkpoint blockade.

Interpretation:

One-carbon metabolism is a critical interface between tumor metabolism and immune response, influencing T-cell fitness and tumor immune evasion.

Limitations:

• Therapeutic strategies must consider the shared metabolic pathways between tumor and immune cells, necessitating context-specific designs.

Conclusion:

Understanding one-carbon metabolism is essential for exploring therapeutic opportunities to enhance immune responses in cancer.