Zhang Yaxiong, Kang Shiyang, Shen Jianfei, He Jiaxi, Jiang Long, Wang Wei, Guo Zhihua, Peng Guilin, Chen Gang, He Jianxing, Liang Wenhua
From the Department of Thoracic Surgery (YZ, SK, JS, JH, LJ, WW, ZG, GP, GC, JH, WL), the First Affiliated Hospital of Guangzhou Medical University; Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease (YZ, SK, JS, JH, LJ, WW, ZG, GP, GC, JH, WL); and Zhongshan School of Medicine (YZ, SK, GC), Sun Yat-sen University, Guangzhou, China.
Medicine (Baltimore). 2015 Feb;94(6):e515. doi: 10.1097/MD.0000000000000515.
The expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients' survival remains controversial.Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33-2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22-5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.
在各种上皮来源的恶性肿瘤中均观察到程序性细胞死亡蛋白1(PD-1)及其配体(PD-L1)的表达。然而,肿瘤细胞上PD-L1的表达或肿瘤浸润淋巴细胞(TILs)上PD-1的表达是否与患者生存相关仍存在争议。检索电子数据库以获取符合条件的文献。提取根据免疫组织化学评估的PD-L1或PD-1表达状态得出的总生存(OS)的风险比(HR)及95%置信区间(CI)的数据。基于随机效应模型对结果进行综合分析。提出亚组分析。纳入了29项研究,涵盖12种上皮来源的恶性肿瘤,涉及7319例患者(PD-L1阳性/阴性分别为2030/3641例,PD-1阳性/阴性分别为505/1143例),这些研究有按PD-L1/PD-1状态分层的结局可用数据。与PD-L1表达阴性的上皮来源癌症患者相比,肿瘤组织中PD-L1表达阳性的患者OS显著更差(HR 1.81,95%CI 1.33 - 2.46,P<0.001)。同样,TILs上PD-1表达阳性的患者OS明显短于PD-1阴性组(HR 2.53,95%CI 1.22 - 5.21,P = 0.012)。在PD-L1分析中,所有亚组均显示PD-L1表达阳性患者预后不良的一致趋势,无论抗体和评估临界值如何。由于数据有限,无法进行PD-1的亚组分析。PD-L1或PD-1表达状态是上皮来源恶性肿瘤的重要预后因素。