Predominance of Th17 over regulatory T-cells in pleural effusions of patients with lung cancer implicates a proinflammatory profile.

Abstract

BACKGROUND: Regulatory T-(Treg) and pro-inflammatory T-helper 17 (Th17) cells have been reported to be involved in the pathogenesis of pleural effusions caused by lung cancer. However, the presence of these subsets might not be a consequence of tumor pathogenesis, but rather a result of the pleural effusion itself, irrespective of its origin. In the present study, we analyzed the balance between these CD4+ T-cell subsets and compared them with those in non-malignant pleural effusions. PATIENTS AND METHODS: We detected the frequencies of Treg and Th17 cells, identified as cluster of differentiation (CD)3+CD4+CD25+CD127low/- and CD3+CD4+ retinoid-related orphan receptor γt (RORγt)+ cells respectively, and proportions of interleukin (IL)17A-producing CD4+ cells in pleural effusions of patients with lung cancer, tuberculous and non-chronic pathologies by flow cytometry. The cytokine profile of stimulated CD4+ T-cells from tuberculosis and cancer groups was compared. RESULTS: The proportion of Th17 cells were increased whereas Tregs were decreased in both tuberculosis and cancer, but not in non-chronic pathologies. Nevertheless, CD4+ T-cells from lung cancer effusions secreted interferon (IFN)γ, IL6 and IL17A, whereas CD4+ T-cells from tuberculous effusions secreted IL10 and low levels of IFNγ. CONCLUSION: Although effusions from patients with chronic pathologies presented higher proportions of Th17 cells in comparison to those with non-chronic pathologies, only Th17 cells from malignant effusions maintained their proinflammatory profile after stimulation. Thus, in the pleural compartment of patients with lung cancer, a proinflammatory environment might be favored and possibly maintained by Th17 response.