Dual Functions of Treg in the Mucosal Barrier and Lung Cancer Microenvironment and Prospects for Targeted Therapy.

Lung cancer remains one of the most common and deadly malignancies worldwide, representing a process intimately associated with dynamic changes in the tumour immune microenvironment. The pulmonary mucosal barrier, which serves as the first line of immune defence against pathogens and exogenous insults, not only restrains excessive inflammation by preserving local immune homeostasis but also actively participates in shaping the lung cancer microenvironment. Regulatory T cells (Tregs) are critical immunosuppressive cells that play a dual role in this context: they sustain immune tolerance by supporting mucosal barrier integrity and preventing autoimmunity, while concurrently mediating immunosuppression within the tumour niche to facilitate immune evasion and disease progression. Although recent years have seen considerable progress in elucidating the roles of the mucosal barrier and Tregs in lung cancer, their molecular regulatory networks and translational potential as therapeutic targets require further systematic investigation. This review synthesises current understanding of the interplay between the mucosal barrier and Tregs in the lung cancer immune microenvironment, with a focus on the functional balance between Treg-mediated immunosuppression and mucosal maintenance. Based on this, we propose an integrative conceptual framework-the "mucosal-Treg-tumor immune axis"-to reconcile the context-dependent duality of Tregs. It also evaluates current strategies and clinical prospects for targeting Tregs and associated signalling pathways in lung cancer immunotherapy, aiming to offer novel perspectives for therapeutic optimisation.