Stromal MTHFD2 Links Fibrotic Remodeling to Immune Evasion via Redox-Dependent Inflammatory Signaling in Lung Adenocarcinoma.

Stromal MTHFD2 drives fibrotic remodeling and immune evasion in lung adenocarcinoma by promoting redox-dependent inflammatory signaling, with high levels linked to poor prognosis.

• Why it matters: Understanding how the tumor microenvironment contributes to immune evasion is crucial for developing effective therapies, especially since fibrosis and immune suppression often coexist in lung adenocarcinoma.
• What they did: The study used single-cell RNA sequencing and experimental models to show that MTHFD2 is elevated in cancer-associated fibroblasts, where its expression is induced by TGF-β and matrix stiffening, and that it regulates inflammatory responses through redox imbalance.
• The result: Targeting MTHFD2 reduced inflammatory cytokine production, tumor growth, and immune evasion markers like PD-L1, suggesting MTHFD2 as a potential therapeutic target to counteract fibrosis-associated immune suppression.