A study published in Nature has identified a regulatory T cell circuit that accumulates in preinvasive lung lesions and can be tracked in peripheral blood, with preclinical experiments showing that disrupting this circuit halved tumor incidence in mice — findings that researchers at University College London (UCL) say may inform ways of intercepting lung cancer before invasion occurs.
The work, led by Dr James Reading of the UCL Cancer Institute and Professor Sam M. Janes of the UCL Division of Medicine, combined multi-omic immune profiling of patients under bronchoscopic and CT surveillance with experiments in a carcinogen-driven mouse model of lung squamous tumorigenesis.
The central finding is that effector regulatory CD4+ T cells (eTreg cells) expressing the transcription factor BATF accumulate in high-grade premalignant airway lesions and are clonally related to circulating eTreg cells, meaning blood levels of these cells rise during preinvasive progression and track disease development. In patients with early-stage non-small cell lung cancer (NSCLC) detected by CT screening, an elevated eTreg cell signature defined rapid disease progression.
The proposed mechanism involves preinvasive lesions conditioning tumor-draining lymph nodes to expand circulating eTreg cells, which converge with locally derived Treg cells at sites of airway dysplasia, forming Treg-rich peribronchial immature tertiary lymphoid structures (iTLSs) that the authors suggest suppress immune clearance of abnormal cells.