A preinvasive regulatory T cell axis for lung cancer interception

Late-stage non-small cell lung cancer (NSCLC) is rarely curable 1 , underscoring a need to intervene earlier in the disease process. Growing evidence suggests that antitumour T cell responses are mounted but become progressively dysregulated during early tumorigenesis 2 , 3 . Tracking and targeting preinvasive T cell regulation may inform new approaches to detect and intercept lung cancer development. Here we explore how the T cell network is remodelled during NSCLC development via multi-omic, cross-tissue immune profiling in patients with preinvasive lung lesions surveilled by autofluorescence bronchoscopy and computed tomography (CT) imaging. Effector regulatory CD4 + T cells (eT reg cells) expressing basic leucine zipper ATF-like transcription factor (BATF) accumulated in high-grade premalignant airway lesions and were clonally related to circulating eT reg cells. Circulating eT reg cells were increasingly elevated during preinvasive progression, enabling lung tumorigenesis to be tracked through analysis of peripheral blood.