PD-L1表达及其对接受EGFR-TKI治疗的EGFR突变型非小细胞肺癌患者临床结局的影响。
PD-L1 expression and its effect on clinical outcomes of EGFR-mutant NSCLC patients treated with EGFR-TKIs.
作者信息
Bai Yuchen, Chen Xiaoxia, Hou Likun, Qian Jun, Jiang Tao, Zhou Caicun, Ciebiada Maciej
机构信息
Department of General and Oncological Pulmonology, University Clinical Hospital Norbert Barlicki, Medical University of Lodz, Lodz 50243, Poland.
Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
出版信息
Cancer Biol Med. 2018 Nov;15(4):434-442. doi: 10.20892/j.issn.2095-3941.2018.0223.
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 ( = 0.020) and marginally associated with higher CD8+ TILs density ( = 0.056). Positive PD-L1 expression was associated with markedly inferior overall survival (OS) in multivariate analysis ( = 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.
目的
据报道，表皮生长因子受体（EGFR）激活会上调肺癌细胞中程序性死亡配体1（PD-L1）的表达，进而导致免疫逃逸，这表明其在EGFR驱动的肺癌中起关键作用。本研究对手术切除的EGFR突变非小细胞肺癌（NSCLC）患者的PD-L1表达进行了特征分析。还在接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的晚期EGFR突变NSCLC患者中研究了PD-L1表达对临床结局的影响。
方法
共纳入73例手术切除的NSCLC且有EGFR突变的患者。通过免疫组织化学评估PD-L1表达和CD8 +肿瘤浸润淋巴细胞（TIL）密度。对评估PD-L1表达在接受EGFR-TKIs治疗的晚期EGFR突变NSCLC患者中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表达呈阳性，这与KRAS伴随突变显著相关（P = 0.020），与较高的CD8 + TILs密度有边缘相关性（P = 0.056）。在多因素分析中，PD-L1表达阳性与总体生存期（OS）显著较差相关（P = 0.032）。PD-L1和CD8 + TILs表达的组合可用于将人群分为三组，其预后不同。对六篇出版物的荟萃分析表明，在接受EGFR-TKIs治疗的晚期EGFR突变NSCLC患者中，PD-L1表达阳性与OS[风险比（HR）= 0.90；95%置信区间（CI），0.42 - 1.38]或无进展生存期（HR = 1.03；95%CI，0.73 - 1.33）无关。
结论
在手术切除的EGFR突变NSCLC中，PD-L1表达倾向于与CD8 + TIL表达、KRAS伴随突变及不良生存相关。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。
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