Xu Yaolin, Cui Guoyuan, Jiang Zhongxiu, Li Ning, Zhang Xiaoye
Department of Oncology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110000, P.R. China.
Oncol Lett. 2019 Mar;17(3):2960-2968. doi: 10.3892/ol.2019.9910. Epub 2019 Jan 9.
Immune checkpoints expressed on tumor cells may suppress the cytotoxicity of tumor-infiltrating lymphocytes (TILs) via interaction with their ligands. In the present study, checkpoint proteins and ligands, including programmed death-1 (PD-1), programmed death ligand-1 (PD-L1), cluster of differentiation (CD)155 and T cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) were systematically analyzed in patients with small cell lung cancer (SCLC). Furthermore their clinicopathological features and survival rates were investigated. Immunohistochemistry was performed in order to analyze the expression of PD-L1, CD155, PD-1 and TIGIT in 60 patients with SCLC, and survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. It was reported that CD155/TIGIT and PD-L1/PD-1 were highly expressed on tissues of surgically resected SCLC. High expression levels of PD-L1, CD155 or PD-L1+CD155 were significantly associated with shorter survival. However, high expression levels of PD-1 or TIGIT exhibited no obvious association with shorter survival time. Moreover, patients with SCLC in whom PD-L1 and CD155 levels were highly expressed had the shortest survival rate. Multivariate survival analysis revealed that highly expressed PD-L1 [hazard ratio (HR)=2.55, 95% confidence interval (CI)=1.18-5.51, P=0.017] and CD155 (HR=2.40, 95% CI=1.05-5.50, P=0.038) were independent prognostic factors for overall survival (OS) time in SCLC. In addition, it was reported that TIGIT and PD-1, the receptors of CD155 and PD-L1, respectively, were also constitutively expressed on CD8 TILs and tumor cells in SCLC. High expression levels of PD-L1 and CD155 were independent prognostic factors for OS time in patients with SCLC.
肿瘤细胞上表达的免疫检查点可能通过与其配体相互作用来抑制肿瘤浸润淋巴细胞（TILs）的细胞毒性。在本研究中，对小细胞肺癌（SCLC）患者的检查点蛋白及其配体进行了系统分析，这些蛋白和配体包括程序性死亡蛋白1（PD-1）、程序性死亡配体1（PD-L1）、分化簇（CD）155以及含有免疫球蛋白和免疫酪氨酸抑制基序结构域的T细胞免疫受体（TIGIT）。此外，还研究了它们的临床病理特征和生存率。采用免疫组织化学方法分析60例SCLC患者中PD-L1、CD155、PD-1和TIGIT的表达情况，并使用Kaplan-Meier法和Cox比例风险模型进行生存分析。结果显示，在手术切除的SCLC组织中，CD155/TIGIT和PD-L1/PD-1高表达。PD-L1、CD155或PD-L1+CD155的高表达水平与较短的生存期显著相关。然而，PD-1或TIGIT的高表达水平与较短的生存时间无明显关联。此外，PD-L1和CD155水平高表达的SCLC患者生存率最短。多因素生存分析显示，高表达的PD-L1[风险比（HR）=2.55，95%置信区间（CI）=1.18-5.51，P=0.017]和CD155（HR=2.40，95%CI=1.05-5.50，P=0.038）是SCLC患者总生存期（OS）的独立预后因素。此外，据报道，分别作为CD155和PD-L1受体的TIGIT和PD-1在SCLC的CD8 TILs和肿瘤细胞上也组成性表达。PD-L1和CD155的高表达水平是SCLC患者OS时间的独立预后因素。
