FoxP3+ Regulatory T Cells in COPD and LC: a potential bridge between the two disease conditions

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BACKGROUND: Regulatory T cells (Tregs) are a subset of CD4+ T lymphocytes that regulate autoimmune responses and maintain immune tolerance. They are characterized by the expression of several markers, most importantly transcription factor Forkhead box P3 (FoxP3), pivotal for their development and suppressive functions. In Chronic Obstructive Pulmonary Disease (COPD) and Lung Cancer (LC), Tregs influence disease progression. In COPD, Treg frequency and function correlate with worsening disease while in LC Tregs maintain peripheral tolerance and hinder anti-tumor immunity. In this study we aim to explore the potential involvement and role of Tregs in the connection between COPD and LC. We want to assess whether the frequency and function of Treg cells could play a role in the development of LC in COPD subjects. METHODS We conducted a prospective study at the Department of Respiratory Diseases in Naples, Italy, enrolling smoker and non-smoker healthy donors, patients with COPD, LC or both COPD-LC. COPD subjects were classified based on the GOLD guidelines. In all subjects we analyzed the frequency of Tregs, their FoxP3 expression levels and suppressive functions on T effector cells. RESULTS We found that Treg cell frequency was reduced in the peripheral blood of LC subjects, probably due to their recruitment in the lungs, while their frequency was increased in COPD/LC patients. Treg suppressive functions on effector T cell proliferation were reduced in COPD-LC subjects compared to patients affected by LC. CONCLUSION These data suggest that FoxP3+ Treg cells play a key role in LC development in COPD subjects understanding the immune-mechanism linking COPD and LC development could offer a promising treatment approach for cancer therapy.

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