1 Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, China.
2 Department of Pneumology, The First Hospital of Jilin University, Changchun, China.
Cancer Biother Radiopharm. 2019 Jun;34(5):325-333. doi: 10.1089/cbr.2018.2672. Epub 2019 Mar 29.
CD4CD25Foxp3 regulatory T (Treg) cell-mediated immunosuppression has been implicated as a crucial mechanism of tumor immune cell escape in nonsmall cell lung cancer (NSCLC). However, little is known concerning the specific role of CD4CD25Foxp3 Treg cells in NSCLC. The aim of this study was to investigate the frequency of circulating CD4CD25Foxp3 Treg cells and their role in NSCLC. The frequencies of Treg, T helper (Th)1, Th2, and Th17 cells in peripheral blood were separately measured in 36 NSCLC patients and 20 healthy controls (HCs) using flow cytometry. Serum cytokine concentrations were determined using cytometric bead arrays. The frequencies of circulating CD4CD25 T cells and CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were significantly higher in advanced-stage NSCLC patients compared with patients with limited-stage NSCLC. The frequencies of circulating CD4CD25Foxp3 and CD4CD25Foxp3 Treg cells were negatively correlated with interleukin (IL)-17, but positively correlated with serum IL-10 levels. In addition, the Th17/CD4CD25Foxp3 Treg cell ratios were negatively correlated with serum cytokeratin 19 fragment (CYFRA 21-1) concentrations in patients with NSCLC. Moreover, coculturing CD4CD25Foxp3 Treg cells and CD14 monocytes resulted in a higher frequency of CD206CD14 M2-like monocytes compared with CD14 monocytes. Elevated circulating CD4CD25Foxp3 Treg cells may be involved in the pathogenesis of NSCLC.
CD4CD25Foxp3 调节性 T（Treg）细胞介导的免疫抑制作用被认为是非小细胞肺癌（NSCLC）中肿瘤免疫细胞逃逸的关键机制。然而，关于 CD4CD25Foxp3 Treg 细胞在 NSCLC 中的具体作用知之甚少。本研究旨在探讨循环 CD4CD25Foxp3 Treg 细胞的频率及其在 NSCLC 中的作用。采用流式细胞术分别检测 36 例 NSCLC 患者和 20 例健康对照者（HCs）外周血中 Treg、辅助性 T 细胞（Th）1、Th2 和 Th17 细胞的频率。采用细胞因子微珠阵列法测定血清细胞因子浓度。晚期 NSCLC 患者外周血中循环 CD4CD25T 细胞及 CD4CD25Foxp3 和 CD4CD25Foxp3 Treg 细胞的频率明显高于局限期 NSCLC 患者。循环 CD4CD25Foxp3 和 CD4CD25Foxp3 Treg 细胞的频率与白细胞介素（IL）-17 呈负相关，与血清 IL-10 水平呈正相关。此外，NSCLC 患者 Th17/CD4CD25Foxp3 Treg 细胞比值与血清细胞角蛋白 19 片段（CYFRA 21-1）浓度呈负相关。此外，与 CD14 单核细胞共培养 CD4CD25Foxp3 Treg 细胞可导致 CD206CD14 M2 样单核细胞的频率高于 CD14 单核细胞。循环 CD4CD25Foxp3 Treg 细胞的升高可能与 NSCLC 的发病机制有关。
