Treg/Th17 imbalance in malignant pleural effusion partially predicts poor prognosis.

Abstract

Accumulating evidence shows that an imbalance in regulatory T cells (Tregs)/T helper IL-17-producing cells (Th17) exists in malignant pleural effusion (MPE). However, the cause of this phenomenon in MPE and the underlying mechanism remain uncertain. The percentages of Tregs and Th17 cells in MPE and parapneumonic effusion (PPE) were determined by flow cytometry. Their specific transcription factors, forkhead box P3 (FoxP3) and retinoic acid-related orphan receptor γt (RORγt); related cytokines, interleukin-6 (IL-6), IL-17, IL-10, and transforming growth factor-β1 (TGF‑β1); and chemokines, C-C motif ligand 17 (CCL17) and CCL20, were analyzed by real-time PCR and ELISA, respectively. Compared to patients with PPE, patients with MPE presented a higher percentage of Tregs but a lower frequency of Th17 cells. Foxp3 mRNA expression level in the cells in the pleural effusion was significantly increased in patients with MPE compared to the levels in patients with PPE (MPE vs. PPE: 3.05±0.62 vs. 0.52±0.11, p=0.0012). It was also noted that high levels of IL-10, TGF-β1 and CCL17 were observed in MPE when compared to PPE (MPE vs. PPE: IL-10, 166.3±39.53 vs. 40.38±10.92 pg/ml, p=0.0307; TGF-β1, 10,720±1,274 vs. 1,747±293.2 pg/ml, p<0.0001; CCL17, 341.1±88.22 vs. 119.2±19.80 pg/ml, p=0.0427). Furthermore, a high ratio of Tregs/Th17 cells in MPE was highly correlated to poor survival. An alteration in CCL17 and CCL20 might contribute to the Treg/Th17 imbalance in MPE, which partially predicts a poor prognosis in patients with lung cancer.