Special T Cell Subsets Involved In Lung Cancer

Part One Treg/Th17 imbalance in malignant pleural effusion partially predicts poor prognosisMalignant pleural effusion (MPE) is a common and devastating complication of various advanced malignancies, of which lung cancer is the most common cause. The incidence of MPE parallels that of lung cancer and its presence impedes effective surgery and is predictive of poor prognosis. Accumulating evidence shows that an imbalance in regulatory T cells (Tregs)/T helper IL-17-producing cells (Th17) exists in 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 yt (RORyt); 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-β1,10,72±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.Part Two IL-17-producing T cells and associated cytokines in lung cancerLung cancer is one of the most common cancers in the world, with an increased mortality rate.Interleukin-17A-producing T cells (IL-17A+T) (as IL-17A+CD4+Th17, IL-17A+CD8+Tc17 and IL-17A+γδT17) and associated cytokines (as IL-17A, IL-23 and IL-1β) play crucial roles in inflammation-associated diseases, such as infection, autoimmunity and tumors. Thl7 cells promote human lung cancer, although the source of intracellular IL-17A and the roles of Tc17 cells and γδT17 cells remain poorly understood. The percentages of Th17 cells, Tc17 cells and γδT17 cells in patients with lung cancer and healthy controls were determined by flow cytometry. Related cytokines, such IL-1β, IL-17, IL-23, and TGF-β1 were analyzed by real-time PCR and ELISA, respectively. In this study, the frequencies of circulating Th17 and γδT17 cells in patients with lung cancer were found to be significantly expanded compared to those in healthy controls; however, Tc17 cells were decreased in these patients. Moreover, IL-17A was found to be produced mainly by Th17 cells in human peripheral blood. Similarly, serum levels and relative mRNA expressions of IL-17A, IL-23, IL-1β and TGF-β1 were significantly increased in patients with lung cancer, and the frequency of Th17 cells was closely associated with serum IL-17A concentrations in these patients. Reducing tumor burden by operation can decreased the frequencies of circulating Th17 cells and y8T17 cells, along with decline of levels of IL-1β, IL-17, IL-23 and TGF-β1, while inversely increased the frequency of circulating Tc17 cells. Taken together, these findings suggested that IL-17A+T cells and associated cytokines might play crucial roles in human lung cancer progression and metastasis and thus represent potential targets for treatment.