Systemic and Tumor Th1 and Th2 Inflammatory Profile and Macrophages in Lung Cancer: Influence of Underlying Chronic Respiratory Disease

Systemic and Tumor Th1 and Th2 Inflammatory Profile and Macrophages in Lung Cancer: Influence of Underlying Chronic Respiratory Disease
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DOI:
10.1016/j.jtho.2016.09.137
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发表时间:
2017-02-01
影响因子:
20.4
通讯作者:
Barreiro, Esther
Barreiro, Esther
中科院分区:
医学1区
文献类型:
--
作者:
Mateu-Jimenez, Merce;Curull, Victor;Barreiro, Esther

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简介:慢性呼吸系统疾病,特别是慢性阻塞性肺病(COPD)和炎症事件是肺癌(LC)的基础。我们假设辅助性T细胞1和辅助性T细胞2细胞因子以及1型和2型巨噬细胞的表达谱(M1和M2)在伴有和不伴有COPD的NSCLC患者的肺肿瘤和血液中差异表达,并且M1/M2比率可能特别影响其存活。在血中,炎性细胞因子采用酶联免疫吸附试验(ELISA)检测80例LC患者血清中(60例LC合并COPD [LC-COPD组]和20例仅LC [仅LC组])和肺标本(肿瘤和非肿瘤)从那些接受开胸手术(LC-COPD组20例,单纯LC组20例)。与单纯LC组相比,LC-COPD组中肿瘤坏死因子-α、白细胞介素-2(IL-2)、转化生长因子-β和IL-10的全身水平升高,而血管内皮生长因子和IL-4水平降低。在肺肿瘤中,LC-COPD组的肿瘤坏死因子-α、转化生长因子-β和IL-10水平高于非肿瘤实质,而仅LC组和LC-COPD组的肿瘤中IL-2和血管内皮生长因子水平均较高。与非肿瘤肺相比,两组患者肿瘤中M1巨噬细胞计数均减少,而M2计数均增加,LC-COPD组的M1/M2比值高于仅LC组。M1和M2计数并没有影响患者的survival.Conclusions:T辅助细胞1细胞因子和M1巨噬细胞在血液和肿瘤的患者与潜在的COPD的相对优势意味着,更强的促炎症模式存在于这些患者。炎症不应该在所有LC患者中系统地靶向。筛查潜在的呼吸系统疾病的存在和识别特定的炎症模式,应进行LC患者,至少在其疾病的早期阶段。(C)2016年国际肺癌研究协会。爱思唯尔公司出版All rights reserved.
Introduction: Chronic respiratory conditions, especially chronic obstructive pulmonary disease (COPD), and inflammatory events underlie lung cancer (LC). We hypothesized that profiles of T helper 1 and T helper 2 cytokines and type 1 and type 2 macrophages (M1 and M2) are differentially expressed in lung tumors and blood of patients with NSCLC with and without COPD and that the ratio M1/M2 specifically may influence their survival.Methods: In blood, inflammatory cytokines (determined by enzyme-linked immunosorbent assay) were quantified in 80 patients with LC (60 with LC and COPD [the LC-COPD group] and 20 with LC only [the LC-only group]) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (20 in the LC-COPD group and 20 in the LC-only group).Results: In the LC-COPD group compared with in the LC only group, systemic levels of tumor necrosis factor-a, interleukin-2 (IL-2), transforming growth factor-beta, and IL-10 were increased, whereas vascular endothelial growth factor and IL-4 levels were decreased. In lung tumors, levels of tumor necrosis factor-a, transforming growth factor-beta, and IL-10 were higher than in nontumor parenchyma in the LC-COPD group, whereas IL-2 and vascular endothelial growth factor levels were higher in tumors of both the LC-only and LC-COPD groups. Compared with in nontumor lung, M1 macrophage counts were reduced whereas M2 counts were increased in tumors of both patient groups, and the M1/M2 ratio was higher in the LC-COPD group than the LC-only group. M1 and M2 counts did not influence patients' survival.Conclusions: The relative predominance of T helper 1 cytokines and M1 macrophages in the blood and tumors of patients with underlying COPD imply that a stronger proinflammatory pattern exists in these patients. Inflammation should not be targeted systematically in all patients with LC. Screening for the presence of underlying respiratory diseases and identification of the specific inflammatory pattern should be carried out in patients with LC, at least in early stages of their disease. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.