Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume.
Research Institute for Disease of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka.
Ann Oncol. 2014 Oct;25(10):1935-1940. doi: 10.1093/annonc/mdu242. Epub 2014 Jul 9.
Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC.
The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry.
Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients.
High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.
最近的临床试验表明，免疫检查点阻断在一部分晚期非小细胞肺癌（NSCLC）患者中产生了临床反应。我们研究了在接受手术切除的 NSCLC 患者中，程序性死亡配体 1（PD-L1）的表达是否与临床病理或预后因素相关。
通过免疫组织化学分析评估了 164 例手术切除的 NSCLC 标本中 PD-L1 的表达。通过流式细胞术定量检测 NSCLC 细胞系中 PD-L1 的细胞表面表达。
肿瘤标本中 PD-L1 的表达在女性中明显高于男性，在从不吸烟者中明显高于吸烟者，在腺癌中明显高于鳞癌。多变量分析显示，表皮生长因子受体基因（EGFR）突变的存在和腺癌组织学与 PD-L1 表达的增加显著相关，这种相关性独立于其他因素。在存在激活型 EGFR 突变的 NSCLC 细胞系中，PD-L1 的细胞表面表达也明显更高。EGFR 抑制剂厄洛替尼下调了前者细胞系中的 PD-L1 表达，但对后者没有影响，表明 PD-L1 的表达是由激活型 EGFR 突变赋予的 EGFR 信号增加所致。在切除的肿瘤组织中高 PD-L1 表达与 NSCLC 患者的总生存期明显缩短相关。
在手术切除的 NSCLC 中，PD-L1 的高表达与 EGFR 突变的存在相关，并且是该疾病的独立负预后因素。
