PD-L1 expression and its effect on clinical outcomes of EGFR-mutant NSCLC patients treated with EGFR-TKIs
PD-L1 expression and its effect on clinical outcomes of EGFR-mutant NSCLC patients treated with EGFR-TKIs
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DOI：
10.20892/j.issn.2095-3941.2018.0223
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发表时间：
2018-11-01
影响因子：
5.5
通讯作者：
Ciebiada, Maciej
中科院分区：
文献类型：
--
作者：
Bai, Yuchen;Chen, Xiaoxia;Ciebiada, Maciej
目的：据报道，表皮生长因子受体（Epidermal growth factor receptor， EGFR）激活可上调肺癌细胞中程序性死亡配体1 （programmed death-ligand 1, PD-L1）的表达，并随后促进免疫逃逸，表明其在EGFR驱动的肺肿瘤中起关键作用。这项研究描述了手术切除egfr突变的非小细胞肺癌（NSCLC）患者中PD-L1的表达。在使用egfr -酪氨酸激酶抑制剂（TKIs）治疗的晚期egfr -突变型NSCLC中，PD-L1表达对临床结果的影响也被研究。方法：共发现73例手术切除的非小细胞肺癌和EGFR突变患者。免疫组化检测PD-L1表达及CD8+肿瘤浸润淋巴细胞（TIL）密度。我们对评估经EGFR-TKIs治疗的晚期egfr -突变NSCLC患者中PD-L1表达的预测和预后价值的出版物进行了文献综述。结果：19例（26.0%）患者PD-L1表达阳性，与KRAS突变相关（P = 0.020），与CD8+ TILs密度升高相关（P = 0.056）。多因素分析显示，PD-L1阳性表达与总生存期（OS）显著降低相关（P = 0.032）。PD-L1和CD8+ TILs的联合表达可用于将人群分为三组，预后不同。对6篇出版物的荟萃分析显示，PD-L1阳性表达与OS无关[风险比(HR) = 0.90；95%可信区间（CI）， 0.42-1.38]或接受EGFR-TKIs的晚期egfr突变NSCLC患者的无进展生存率（HR = 1.03; 95 CI, 0.73-1.33）。结论：在手术切除的egfr突变型非小细胞肺癌中，PD-L1表达倾向于与CD8+ TIL表达、伴随的KRAS突变和较差的生存率相关。在接受EGFR-TKIs治疗的晚期egfr突变NSCLC患者中，PD-L1表达既不是预测因素，也不是预后因素。
Objective: Epidermal growth factor receptor (EGFR) activation was reported to upregulate programmed death-ligand 1 (PD-L1) expression in lung cancer cells and subsequently contribute to immune escape, indicating its critical role in EGFR-driven lung tumors. This study characterized PD-L1 expression in patients with surgically resected EGFR-mutant non-small cell lung cancer (NSCLC). The effect of PD-L1 expression on clinical outcomes was also investigated in advanced EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKIs).Methods: In total, 73 patients with surgically resected NSCLC and EGFR mutations were identified. PD-L1 expression and CD8+ tumor-infiltrating lymphocyte (TIL) density were assessed by immunohistochemistry. A literature review of publications that assessed the predictive and prognostic value of PD-L1 expression in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs was performed.Results: Nineteen (26.0%) patients were positive for PD-L1 expression, which was significantly associated with concomitant KRAS mutation (P = 0.020) and marginally associated with higher CD8+ TILs density (P = 0.056). Positive PD-L1 expression was associated with markedly inferior overall survival (OS) in multivariate analysis (P = 0.032). The combination of PD-L1 and CD8+ TILs expression could be used to stratify the population into three groups with distinct prognoses. A meta-analysis of six publications showed that positive PD-L1 expression was not associated with OS [hazard ratio (HR) = 0.90; 95% confidence interval (CI), 0.42-1.38] or progression-free survival (HR = 1.03; 95 CI, 0.73-1.33) in advanced EGFR-mutant NSCLC patients receiving EGFR-TKIs.Conclusions: PD-L1 expression tended to correlate with CD8+ TIL expression, concomitant KRAS mutation, and poor survival in surgically resected EGFR-mutant NSCLC. PD-L1 expression was neither the predictive nor the prognostic factor in advanced EGFR-mutant NSCLC patients treated with EGFR-TKIs.