Wang Kaiyuan, Wang Jian, Wei Feng, Zhao Ning, Yang Fan, Ren Xiubao
Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Front Immunol. 2017 Apr 21;8:456. doi: 10.3389/fimmu.2017.00456. eCollection 2017.
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, = 0.041), increased clinical TNM stage ( < 0.001), and presence of lymphatic invasion ( < 0.001). Besides, TLR4 expression level in cancer samples was inversely correlated with serum sTLR4 level in patients with early-stage NSCLC ( = -0.485, = 0.003). TLR4 expression level was also positively correlated with the PD-L1 expression level ( = 0.545, < 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.
目前，炎症对肿瘤发生和进展的影响已受到广泛关注。作为模式识别受体的一员，Toll样受体4（TLR4）在肿瘤免疫微环境中起关键作用，且对其研究日益增多。在本研究中，我们评估了非小细胞肺癌（NSCLC）组织中TLR4的表达及其与程序性细胞死亡配体1（PD-L1）的关系，并评估了TLR4对术后结局的预测价值。纳入了2008年4月至2014年8月期间接受全肺切除和系统性淋巴结清扫的126例NSCLC患者。所有患者均有完整的临床病理记录和随访数据。通过免疫组织化学测定NSCLC样本中TLR4和PD-L1的表达，通过酶联免疫吸附测定法测量血清可溶性TLR4（sTLR4）水平。结果显示，癌组织中TLR4表达水平显著高于癌旁组织。TLR4表达升高与组织学类型（腺癌高于鳞癌，P = 0.041）、临床TNM分期增加（P < 0.001）和存在淋巴浸润（P < 0.001）显著相关。此外，早期NSCLC患者癌样本中TLR4表达水平与血清sTLR4水平呈负相关（r = -0.485，P = 0.003）。TLR4表达水平也与PD-L1表达水平呈正相关（r = 0.545，P < 0.0001）。多因素分析显示，TLR4表达水平是独立的预后因素，TLR4过表达提示总生存期和无病生存期较差。综上所述，我们得出结论，肺癌中TLR4的表达与PD-L1相关，并且可以预测接受肺癌肺切除患者的预后。
