PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.
PD-1 and PD-L1 Expression in NSCLC Indicate a Favorable Prognosis in Defined Subgroups.
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DOI：
10.1371/journal.pone.0136023
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hartmann W
中科院分区：
文献类型：
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作者：
Schmidt LH;Kümmel A;Görlich D;Mohr M;Bröckling S;Mikesch JH;Grünewald I;Marra A;Schultheis AM;Wardelmann E;Müller-Tidow C;Spieker T;Schliemann C;Berdel WE;Wiewrodt R;Hartmann W
免疫治疗可以成为改善肺癌患者预后的重要治疗选择。针对程序性细胞死亡受体PD-1及其配体PD-L1的治疗的首次临床试验在几种实体肿瘤中显示出有希望的结果。然而，在肺癌中，这些免疫因子的诊断、预后和预测价值尚不清楚。在一项321例临床注释良好的非小细胞肺癌（NSCLC）患者的研究中，使用免疫组织化学方法评估了这两个因素的影响。肿瘤浸润淋巴细胞（til）表达PD-1的比例为22%，而肿瘤细胞相关的PD-L1表达比例为24%。Fisher精确检验发现PD-L1和Bcl-xl蛋白表达呈正相关（p = 0.013）。有趣的是，肿瘤细胞上的PD-L1表达与肺鳞状细胞癌（SCC, p = 0.042， log rank检验）、辅助治疗（p = 0.017）、肿瘤大小增加（pn1 -4, p = 0.039）和淋巴结状态阳性（pN1-3, p = 0.010）的总生存率提高相关。这些观察结果被多变量cox回归模型证实。我们研究的一个主要发现是确定了PD-L1在肺SCC患者亚群中的预后意义，肿瘤大小增加，淋巴结状态阳性和接受辅助治疗的非小细胞肺癌患者。该研究为非小细胞肺癌患者的免疫环境相关风险分层提供了第一个数据。需要进一步的研究来证实这一观察结果，并在PD-1抑制的背景下评估PD-1和PD-L1在NSCLC中的预测价值。
Immunotherapy can become a crucial therapeutic option to improve prognosis for lung cancer patients. First clinical trials with therapies targeting the programmed cell death receptor PD-1 and its ligand PD-L1 have shown promising results in several solid tumors. However, in lung cancer the diagnostic, prognostic and predictive value of these immunologic factors remains unclear. The impact of both factors was evaluated in a study collective of 321 clinically well-annotated patients with non-small lung cancer (NSCLC) using immunohistochemistry. PD-1 expression by tumor infiltrating lymphocytes (TILs) was found in 22%, whereas tumor cell associated PD-L1 expression was observed in 24% of the NSCLC tumors. In Fisher’s exact test a positive correlation was found for PD-L1 and Bcl-xl protein expression (p = 0.013). Interestingly, PD-L1 expression on tumor cells was associated with improved overall survival in pulmonary squamous cell carcinomas (SCC, p = 0.042, log rank test), with adjuvant therapy (p = 0.017), with increased tumor size (pT2-4, p = 0.039) and with positive lymph node status (pN1-3, p = 0.010). These observations were confirmed by multivariate cox regression models. One major finding of our study is the identification of a prognostic implication of PD-L1 in subsets of NSCLC patients with pulmonary SCC, with increased tumor size, with a positive lymph node status and NSCLC patients who received adjuvant therapies. This study provides first data for immune-context related risk stratification of NSCLC patients. Further studies are necessary both to confirm this observation and to evaluate the predictive value of PD-1 and PD-L1 in NSCLC in the context of PD-1 inhibition.