Disturbed Th17/Treg Balance in Patients with Non-small Cell Lung Cancer

Abstract

The fine balance of T help-17 (Th17)/regulatory T(Treg) cells is crucial for maintenance of immune homeostasis. However, there is little information concerning the role played in non-small cell lung cancer (NSCLC) by Th17/Treg cells. The objective of this study was to investigate the variation of Th17 and Treg cells in the peripheral blood of patients with NSCLC. Blood samples were collected from 19 patients with NSCLC and 19 healthy donors. Samples were processed to detect CD4(+)IL-17(+) Th17 cells and CD4(+)CD25(+)Foxp3(+) Treg cells by flow cytometry, and related gene expressions were assessed by real-time quantitative polymerase chain reaction. The concentrations of interleukin (IL)-1β, IL-6, IL-10, IL-17, IL-23, and transforming growth factor-beta (TGF-β1) were also measured by enzyme-linked immunosorbent assay analysis (ELISA). The frequency of circulating Th17 cells and Treg cells was increased in samples derived from patients with NSCLC, accompanied by the upregulation of Foxp3 and RORγt. However, a negative correlation between Treg cells and Th17 cells was found in patients with NSCLC. Additionally, the Th17/Treg ratio and the related cytokines were also significantly higher in patients with NSCLC than in healthy controls. Furthermore, the frequency of Th17 cells was positively correlated with IL-1β, IL-6, and IL-23 in patients with NSCLC, and the frequency of Treg cells was positively correlated with TGF-β1 and IL-10. More importantly, the Th17/Treg ratio was positively correlated with the CEA concentrations in patients with NSCLC. Our data indicated that Th17 and Treg subset are involved in the immunopathology of NSCLC. Distinct cytokine environment might play a key role in the differentiation of the Th17 and Treg cells in NSCLC. Reconstituting an adequate balance between Th17 and Treg may be beneficial in the treatment of NSCLC.

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

“…Importantly, plasma IL-23 concentrations in the Chinese study (ranging between 0.05 ng/mL in healthy controls up to 0.25 ng/mL in NSCLC) were well below the controversial anti-tumorigenic levels as obvserved by Li et al [31]. A second study confirmed similar levels of IL-23 in healthy controls and lung cancer patients [62]. One of the current weaknesses in this regard is that present data for serum IL-23 levels have mostly or exclusively been generated in Asian populations.…”

“…It remains unclear to what extent TregFoxP3+ and Th17 cells are contrarian players in NSCLC when looking at the data of Li and colleagues [61]. Duan and colleagues found higher circulating Th17 cells and Treg cells in NSCLC patients compared to healthy controls, supporting the hypothesis that Th17 and Treg cells are involved in the immunopathology of NSCLC [62].…”

Emerging roles of T helper 17 and regulatory T cells in lung cancer progression and metastasis

“…Peripheral blood of NSCLC patients is characterized by a significantly higher percentage of Th17 (CD4 + IL-17 + ) and Treg cells (CD4 + CD25 + FoxP3 + ) compared to individuals without cancer. However, in NSCLC patients, the levels of these two CD4 + T cell subsets were inversely correlated in peripheral blood [137] (Fig. 6).…”

“…6). Serum Th17 cells are known to positively correlate with IL-1β, IL-6, IL-23, while Tregs are known to positively correlate with TGF-β1 and IL-10 [137] (Fig. 6).…”

“…6). Conversely, the ratio was determined in another study to inversely correlate with serum levels of carcinoembryonic antigen (CEA), an oncofetal marker elevated in lung cancers with poor prognosis [137]. These studies highlight the variability of CD4 + T cell ratios in cancer progression, which certainly warrants further exploration [126].…”