A preinvasive regulatory T cell axis for lung cancer interception.

Clonally related effector regulatory T cells (eT reg cells) form a preinvasive network across tissues that predicts early lung cancer progression, with a significant increase during NSCLC development.

• Why it matters: Early detection and intervention in lung cancer are critical, as late-stage NSCLC is rarely curable, but current methods lack effective strategies to target preinvasive immune regulation.
• What they did: Multi-omic immune profiling of patients and mouse models revealed that eT reg cells expressing BATF accumulate in high-grade premalignant lesions and circulate increasingly during disease progression, enabling tracking of tumorigenesis.
• The result: Targeting this eT reg cell axis with PI3Kδ inhibition reduced T reg cells, enhanced immune responses, and decreased tumor incidence, offering a promising approach for early lung cancer interception.