2016年12月4日-7日，第17届世界肺癌大会（WCLC）在奥地利维也纳盛大召开。会议进行到第4天（当地时间的7日上午），公布了4项重要免疫治疗研究成果。
来自古斯塔夫•鲁西癌症校园的Julien Adam教授针对4种PD-L1检测方法（22C3,28-8,SP263,LDT），牵头进行了对比研究，在此次大会上报告了对比结果。
研究背景
PD-L1免疫组化检测（IHC）目前已经成为大多数非小细胞肺癌（NSCLC）抗PD-1/PD-L1治疗的预测标志物，但是在不同的临床试验所用的检测方法不同。有一些研究在中心实验室的专门平台上比较了4种检测方法（22C3,28-8,SP142,SP263）。
为了使PD-L1检测结果统一并适用于大多数IHC平台和中心，研究者比较了下列几种检测方法：PD-L1 Dako（22C3,28-8）、Ventana（SP263）和实验室开发的检测（Laboratory-developed Tests,LDT）。
研究内容
研究在7个医疗中心中，针对41例NSCLC手术标本进行5种抗PD-L1克隆的免疫组化检测，分别是：28-8，22C3，E1L3N，SP412，SP263。
IHC平台包括Ventana BenchMark Ultra（2个中心），Leica Bond（2个中心），Dako Autostainer Link 48（3个中心）。
对于匹配的平台，可以开展22C3，28-8和SP263检测；对于非匹配平台和其他抗体，每个医疗中心可以自己开发实验室检测并在扁桃体组织染色的基础上进行统一。
经过不同的中心和抗体，每个样本都染色了35次。结果由7位胸科病理专家经过PD-L1评分训练后对样本进行分析，每个专家分析6例样本。
肿瘤细胞和免疫细胞PD-L1染色结果采取半定量评分（Dako和Ventana检测推荐）。统计分析为肿瘤细胞设定1%，5%，25%，50%的阈值，为免疫细胞设定1%，5%，10%的阈值。
主要结果
根据Ventana平台（2个）和Dako平台（3个）的分析结果，28-8，22C3和SP263检测在肿瘤细胞和免疫细胞染色方面高度一致。
与上述3个检测相比，LDT检测的一致性水平存在变化。例如使用SP263克隆可以在免疫细胞和肿瘤细胞染色方面与其他平台达到良好的一致性，而其他经选择的LDT联合28-8，22C3和E1L3N克隆只能在肿瘤细胞染色方面与上述3个检测有很好的关联。
结论
不同平台上，28-8，22C3和SP263检测在肿瘤细胞染色方面的结果具有可比性。同样，在一些选择的实验室开发的检测方案下，28-8，22C3，SP263和E1L3N的肿瘤细胞染色也较为一致。
这些结果需要在更大规模的基础上进行验证，以提供NSCLC免疫治疗前PD-L1检测的推荐方法。
摘要原文
Multicentric French Harmonization Study for PD–L1 IHC Testing in NSCLC
Background: PD-L1 immunohistochemistry (IHC) is considered as a predictive biomarker for most anti PD-1/PDL-1 therapies in non-small cell lung cancer, but different assays were used in clinical trials. Several studies have compared 4 assays (22C3, 28-8, SP142, SP263) performed in central laboratories on dedicated platforms. In order to harmonise and make PD-L1 testing widely available on most IHC platforms and centers, we compared PD-L1 Dako (22C3, 28-8) and Ventana (SP263) assays and laboratory-developed tests (LDT).
Methods: IHC with five anti-PD-L1 clones (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers. The IHC platforms used were Ventana BenchMark Ultra (2 centers), Leica Bond (2 centers) or Dako Autostainer Link 48 (3 centers). For each matching platform, 22C3, 28.8 and SP263 assays were performed. For non-matching platforms and other antibodies, LDT were developed in each center and harmonised based on tonsil tissue staining. A total of 35 stainings were performed across different platforms and antibodies for each case. Seven thoracic pathologists trained to PD-L1 scoring in expert courses participated. Each pathologist analysed 6 cases and compared the stainings obtained with the 5 antibodies on all platforms. Tumor cell and immune cell D-L1 stainings were scored semi-quantitatively as recommended in PD-L1 Dako and Ventana assays. For statistical analysis, 1, 5, 25, 50% and 1, 5, 10% thresholds were used for tumor cells and immune cells, respectively.
Results: 28-8, 22C3 and SP263 assays were highly concordant for tumor cell and immune cell stainings across the 5 Dako or Ventana platforms (R2=0.886 to 0.953). LDT demonstrated various levels of concordance as compared to those 3 assays. Notably, LDT using SP263 clone were the most concordant across all platforms for both immune cell and tumor cell stainings, whereas some selected LDT with clones 28-8, 22C3 and E1L3N, but not SP142, showed a good correlation with the 3 assays regarding tumor cells only.
Conclusion: 28-8, 22C3 and SP263 assays gave comparable results across dedicated platforms for tumor cells staining, as well as some selected LDT protocols using 28-8, 22C3, SP263 and E1L3N clones. These results will be further validated at the national level in order to provide recommendations for the use of assays and LDT for PD-L1 testing in NSCLC.
