Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy.
Expression of TLR4 in Non-Small Cell Lung Cancer Is Associated with PD-L1 and Poor Prognosis in Patients Receiving Pulmonectomy.
复制标题
非小细胞肺癌中 TLR4 的表达与 PD-L1 以及接受肺切除术的患者预后不良相关
DOI：
10.3389/fimmu.2017.00456
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发表时间：
2017
影响因子：
7.3
通讯作者：
Ren X
中科院分区：
文献类型：
--
作者：
Wang K;Wang J;Wei F;Zhao N;Yang F;Ren X
目前，炎症对肿瘤发生和发展的影响已被广泛关注。Toll样受体4（TLR 4）作为模式识别受体中的一员，在肿瘤免疫微环境中起着关键作用，近年来受到越来越多的研究。本研究旨在探讨TLR 4在非小细胞肺癌（NSCLC）组织中的表达及其与程序性细胞死亡配体1（PD-L1）的相关性，并评估TLR 4对NSCLC术后预后的预测价值。共入组了126例在2008年4月至2014年8月期间接受完全肺切除术和系统性淋巴结清扫术的NSCLC患者。所有患者均有完整的临床病理资料和随访资料。免疫组化法检测NSCLC组织中TLR 4和PD-L1的表达，酶联免疫吸附法检测血清可溶性TLR 4（sTLR 4）水平。结果表明，癌组织中TLR 4的表达水平显著高于癌旁组织。TLR 4的高表达与组织学类型（腺癌高于鳞癌，P = 0.041）、临床TNM分期（P < 0.001）和淋巴管浸润（P < 0.001）显著相关。此外，在早期NSCLC患者中，肿瘤样本中TLR 4表达水平与血清sTLR 4水平呈负相关（r =-0.485，P = 0.003）。TLR 4表达水平与PD-L1表达水平呈正相关（r = 0.545，P < 0.0001）。多因素分析显示，TLR 4表达水平是独立的预后因素，TLR 4过表达者总生存期和无病生存期均较差。综上所述，我们得出结论，肺癌中TLR 4的表达与PD-L1相关，并且可以预测接受肺切除术的NSCLC患者的预后。
Currently, the effect of inflammation on tumorigenesis and progression has been widely noted. As a member of pattern recognition receptors, toll-like receptor 4 (TLR4) plays a pivotal role in tumor immune microenvironment and has been increasingly investigated. In the present study, we evaluated TLR4 expression and its association with programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) tissues and assessed the predicting value of TLR4 on postoperative outcome. A total of 126 NSCLC patients receiving complete pulmonary resection and systematic lymph node dissection between April 2008 and August 2014 were enrolled. All the patients had integrated clinicopathological records and follow-up data. TLR4 and PD-L1 expression on NSCLC samples were determined by immunohistochemistry, and serum soluble TLR4 (sTLR4) levels were measured by enzyme-linked immunosorbent assay. Results showed that TLR4 expression level in cancer tissue was significantly higher than that in para-cancer tissue. Elevated TLR4 expression was significantly associated with histological type (adenocarcinoma higher than squamous cell carcinoma, P = 0.041), increased clinical TNM stage (P < 0.001), and presence of lymphatic invasion (P < 0.001). Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC (r = −0.485, P = 0.003). TLR4 expression level was also positively correlated with the PD-L1 expression level (r = 0.545, P < 0.0001). Multivariate analysis showed that expression level of TLR4 was an independent prognostic factor and TLR4 overexpression indicated a poor overall survival and disease-free survival. Taken together, we conclude that expression of TLR4 in lung cancer is associated with PD-L1 and could predict the outcome of patients with NSCLC receiving pulmonary resection for cancer.