恶性胸膜间皮瘤（MPM）中程序性细胞死亡1配体1（PD-L1）表达的分析
Analysis of expression of programmed cell death 1 ligand 1 (PD-L1) in malignant pleural mesothelioma (MPM).
作者信息
Cedrés Susana, Ponce-Aix Santiago, Zugazagoitia Jon, Sansano Irene, Enguita Ana, Navarro-Mendivil Alejandro, Martinez-Marti Alex, Martinez Pablo, Felip Enriqueta
机构信息
Medical Oncology Service/Vall d´Hebron Institute Oncology, Vall d'Hebron University Hospital, Barcelona, Spain.
Medical Oncology Service/ 12 de Octubre University Hospital, Madrid, Spain.
出版信息
PLoS One. 2015 Mar 16;10(3):e0121071. doi: 10.1371/journal.pone.0121071. eCollection 2015.
BACKGROUND
The increasing incidence and poor outcome associated with MPM requires finding effective treatment for this disease. PD1/PD-L1 pathway plays a central role in tumor immune evasion and appears to be predictive and prognostic marker. PD-L1 is expressed in many different human cancers but its role in MPM has yet to be established. The aim of this study is to evaluate the expression of PD-L1 in MPM.
METHODS
119 MPM patients (p) from two institutions between November 2002 and February 2014 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained with anti-PD-L1 (clone E1L3N). Cases showing more than 1% of tumor cells expression of PD-L1 were considered positive.
RESULTS
PD-L1 was analyzed in 77 p with tumor tissue available and was positive in 20.7% p (14 samples in membrane, 16 in cytoplasm and 4 in immune infiltrate). PD-L1 intensity was weak in 56.2%, moderate in 25% and strong in 18.7% p. There was a significant relationship between PD-L1 expression and histology (PD-L1 expression 37.5% in no-epithelioid tumor and 13.2% in epithelioid; p=0.033). The median survival in p PD-L1 positive was 4.79 vs 16.3 months in p PD-L1 negative (p=0.012).
CONCLUSIONS
We have shown PD-L1 is expressed in 20% of patients, associated with no epithelioid histology and poor prognostic in MPM. Our results suggest PD-L1 warrants further exploration in selecting p for immunotherapy.
背景
恶性胸膜间皮瘤（MPM）发病率不断上升且预后不佳，需要找到针对该疾病的有效治疗方法。程序性死亡受体1（PD1）/程序性死亡配体1（PD-L1）通路在肿瘤免疫逃逸中起核心作用，似乎是预测和预后标志物。PD-L1在多种不同的人类癌症中表达，但其在MPM中的作用尚未明确。本研究旨在评估PD-L1在MPM中的表达情况。
方法
回顾了2002年11月至2014年2月期间来自两家机构的119例MPM患者。用抗PD-L1（克隆号E1L3N）对福尔马林固定、石蜡包埋的组织进行染色。PD-L1表达超过1%肿瘤细胞的病例被视为阳性。
结果
对77例有肿瘤组织的患者进行了PD-L1分析，20.7%的患者呈阳性（14例样本为膜表达，16例为胞质表达，4例为免疫浸润表达）。PD-L1强度在56.2%的患者中较弱，25%的患者中为中等强度，18.7%的患者中为强强度。PD-L1表达与组织学之间存在显著关系（非上皮样肿瘤中PD-L1表达为37.5%，上皮样肿瘤中为13.2%；p = 0.033）。PD-L1阳性患者的中位生存期为4.79个月，而PD-L1阴性患者为16.3个月（p = 0.012）。
结论
我们发现20%的患者表达PD-L1，其与非上皮样组织学相关，且在MPM中预后较差。我们的结果表明，PD-L1在选择免疫治疗患者方面值得进一步探索。
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