Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
Clin Cancer Res. 2016 Feb 1;22(3):704-13. doi: 10.1158/1078-0432.CCR-15-1543. Epub 2015 Sep 25.
Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC).
A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC.
PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis.
Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors.
程序性死亡配体 1（PD-L1；也称为 CD274 或 B7-H1）的表达代表了癌症免疫逃逸的一种机制。我们的目的是描述原发性喉鳞状细胞癌（SCC）中的肿瘤 PD-L1 表达和相关 T 细胞浸润。
对 260 例可手术的原发性喉 SCC [福尔马林固定石蜡包埋（FFPE）标本]进行了形态学特征分析，包括基质肿瘤浸润淋巴细胞（TIL），在苏木精/伊红染色的全切片上进行，并在 FFPE 标本中通过 qRT-PCR 检测 PD-L1 mRNA 表达。对于 PD-L1 蛋白表达，在由这些肿瘤的两个核心组成的组织微阵列上应用自动定量蛋白分析（AQUA）。此外，在另一组 89 例原发性喉 SCC 患者的新鲜冷冻肿瘤和正常相邻组织标本中评估了 PD-L1 mRNA 表达。
与周围正常组织相比，肿瘤中 PD-L1 mRNA 水平上调（P = 0.009）。TIL 密度与肿瘤 PD-L1 AQUA 水平相关（P = 0.021）。高 TIL 密度和高 PD-L1 AQUA 水平均与更好的无病生存（DFS；TIL：P = 0.009 和 PD-L1：P = 0.044）和总生存（OS；TIL：P = 0.015 和 PD-L1：P = 0.059）显著相关，并且在多变量分析中仍然具有重要意义。
增加的 TIL 密度和 PD-L1 水平与喉鳞状细胞癌的更好结局相关。评估 TIL 和 PD-L1 表达可能有助于预测对免疫检查点抑制剂的反应。
