Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer
Biphasic prognostic significance of PD-L1 expression status in patients with early- and locally advanced-stage non-small cell lung cancer
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DOI：
10.1007/s00262-020-02755-w
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发表时间：
2020-10-28
影响因子：
5.8
通讯作者：
Daigo, Yataro
中科院分区：
文献类型：
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作者：
Teramoto, Koji;Igarashi, Tomoyuki;Daigo, Yataro
肿瘤细胞上的程序性细胞死亡配体 1 (PD-L1) 表达是由干扰素-γ 诱导的，表明诱导了抗肿瘤免疫反应。反过来，PD-L1 与程序性细胞死亡 1 (PD-1) 的结合会触发免疫检查点通路，从而促进肿瘤生长。尽管仍有待阐明，但 PD-L1 表达的临床意义可能随着非小细胞肺癌 (NSCLC) 的肿瘤进展而变化。对接受 I-IIIA 期 NSCLC 根治性手术的患者 (n = 228) 的肿瘤标本进行 PD-L1 免疫组织化学分析。对肿瘤 PD-L1 表达强度进行半定量评分，并根据病理分期评估其与各种临床病理特征和术后无复发生存期 (RFS) 的相关性。在 I 期，与低 PD-L1 评分的患者相比，高 PD-L1 评分的患者术后 RFS 显着延长，5 年无复发概率分别为 94.1% 和 75.1%（P = 0.031）。多变量分析显示，高 PD-L1 评分是术后 RFS 较长的预后因素（风险比：0.111，P = 0.033）。相反，在II期和IIIA期，PD-L1评分高的患者往往会出现术后肿瘤复发。在早期 NSCLC 中，肿瘤 PD-L1 的高表达状态是预测根治性手术后良好预后的生物标志物，并可能反映抗肿瘤免疫反应的诱导。然而，在局部晚期NSCLC中，肿瘤PD-L1表达状态可能反映免疫检查点通路的执行情况并预测术后肿瘤复发的发生率。
Programmed cell death-ligand 1 (PD-L1) expression on tumor cells is induced by interferon-gamma, suggesting the induction of an anti-tumor immune response. In turn, binding of PD-L1 to programmed cell death 1 (PD-1) triggers an immune checkpoint pathway that contributes to tumor growth. Though it remains to be elucidated, the clinical significance of PD-L1 expression might vary with tumor progression in non-small-cell lung cancer (NSCLC). Immunohistochemical analysis of PD-L1 was done in tumor specimens from patients who underwent radical surgery for stage I-IIIA NSCLC (n = 228). Tumor PD-L1 expression intensity was semi-quantitatively scored and its correlation with various clinicopathological features and postoperative relapse-free survival (RFS) was assessed relative to pathological stage. In stage I, postoperative RFS was significantly prolonged in patients with a high PD-L1 score compared with a low PD-L1 score, exhibiting 5-year relapse-free probabilities of 94.1% and 75.1%, respectively (P = 0.031). A multivariate analysis revealed that a high PD-L1 score was a prognostic factor of longer postoperative RFS (hazard ratio: 0.111, P = 0.033). Conversely, in stages II and IIIA, patients with a high PD-L1 score tended to suffer from postoperative tumor recurrence. In early-stage NSCLC, high tumor PD-L1 expression status represents a biomarker to predict good prognosis after radical surgery and may reflect the induction of an antitumor immune response. However, in locally advanced stage NSCLC, tumor PD-L1 expression status may reflect the execution of an immune checkpoint pathway and predicts the incidence of postoperative tumor recurrence.