Regulatory T cell network linked to preinvasive lung cancer progression

Researchers investigated early immune changes in non-small cell lung cancer using multi-omic, cross-tissue profiling of patients with preinvasive lung lesions monitored by autofluorescence bronchoscopy and CT imaging, alongside carcinogen-driven mouse models. The Nature report examined regulatory T cell changes during progression and tested immune interception in mice. Sample sizes and quantitative effect estimates were not provided in the supplied abstract.

Effector regulatory CD4+ T cells expressing BATF accumulated in high-grade premalignant airway lesions and were clonally related to circulating effector regulatory T cells. Blood levels increased during preinvasive progression, and the coordinated cell network was associated with rapid progression in patients with CT-detected early-stage NSCLC. Mice developed a similar network across blood, airways and draining lymph nodes, with expansion of lung BATF-positive regulatory T cells and regulatory T cell-rich immature tertiary lymphoid structures.

In mice, PI3Kδ inhibition prevented formation of these lymphoid structures, reduced blood and lung regulatory T cells, increased local conventional type 1 dendritic cells, and reduced tumour incidence and size. The findings identify potential blood-based markers and an experimental interception target. However, the human findings are observational, and the intervention results are confined to mice; neither clinical monitoring performance nor preventive efficacy in humans is established by the supplied material.