Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Departments of Medicine, Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Lung Cancer. 2018 Nov;125:115-120. doi: 10.1016/j.lungcan.2018.09.004. Epub 2018 Sep 12.
Herpes Virus Entry Mediator (HVEM) is an important immune checkpoint in cancer recognition. HVEM expressed on tumor cell membranes activates immune cell signaling pathways leading to either inhibition of activity (B- and T-lymphocyte attenuator, BTLA) or activation of immune activity (LIGHT). The aim of this study is to investigate the prevalence of HVEM expression and its association with PDL1 expression in NSCLC.
A TMA of 527 resected NSCLC samples and 56 NSCLC cell lines were evaluated for HVEM and PD-L1 expression. The IHC assay for HVEM was optimized on the Dako Link48 autostainer using a polyclonal antibody from R&D Systems(AF356). PD-L1 IHC was performed on the Dako Link48 autostainer using the PD-L1 28-8 pharmDx kit. Scoring HVEM employed the H-score system while for PD-L1 the tumor proportion score (TPS) was used.
HVEM expression in the NSCLC resected samples and cell lines revealed a positive H-score more than 1 was 18.6% (77/415) and 48.2% (27/56) respectively. HVEM expression was significantly higher in patients with lymph node N2 metastasis (25.5% vs 7.9% vs 17.5%, p = 0.046) when comparing with N1 or no lymph node metastasis, and was marginally significantly higher in patients with stage III/IV disease (24.5% vs 16.4%, p = 0.059). Subgroup analysis showed that HVEM (median 45 vs 36 months, p = 0.706) and PD-L1 expression (median 45 vs 48 months, p = 0.178) status was not predictive of overall survival. HVEM was found to have a significant negative correlation with PD-L1 expression (r=-0.274, p < 0.001) in patients with NSCLC and also a weak negative correlation in NSCLC cell lines (r=-0.162, p = 0.352).
HVEM was found to be overexpressed in NSCLC patients of N2 lymph node metastasis or later stage and has a negative co-relationship with PD-L1 expression. HVEM was not prognostic for NSCLC patients.
疱疹病毒进入介体 (HVEM) 是癌症识别中的一个重要免疫检查点。肿瘤细胞膜上表达的 HVEM 激活免疫细胞信号通路，导致活性抑制（B 和 T 淋巴细胞衰减因子，BTLA）或免疫活性激活（LIGHT）。本研究旨在探讨 NSCLC 中 HVEM 表达的流行率及其与 PDL1 表达的相关性。
评估了 527 例 NSCLC 切除标本和 56 例 NSCLC 细胞系的 HVEM 和 PD-L1 表达。使用来自 R&D Systems 的多克隆抗体（AF356）在 Dako Link48 自动染色机上优化 HVEM 的免疫组化检测。使用 PD-L1 28-8 pharmDx 试剂盒在 Dako Link48 自动染色机上进行 PD-L1 IHC。HVEM 评分采用 H 评分系统，PD-L1 采用肿瘤比例评分（TPS）。
在 NSCLC 切除样本和细胞系中，HVEM 表达的阳性 H 评分大于 1 分别为 18.6%（77/415）和 48.2%（27/56）。与无淋巴结转移或 N1 淋巴结转移相比，有淋巴结 N2 转移的患者 HVEM 表达明显更高（25.5%比 7.9%比 17.5%，p=0.046），而在 III/IV 期疾病患者中则略高（24.5%比 16.4%，p=0.059）。亚组分析显示，HVEM（中位 45 个月比 45 个月，p=0.706）和 PD-L1 表达（中位 45 个月比 48 个月，p=0.178）状态与总生存无关。在 NSCLC 患者中，HVEM 与 PD-L1 表达呈显著负相关（r=-0.274，p<0.001），在 NSCLC 细胞系中也呈弱负相关（r=-0.162，p=0.352）。
HVEM 在 N2 淋巴结转移或更晚期的 NSCLC 患者中过表达，并与 PD-L1 表达呈负相关。HVEM 对 NSCLC 患者无预后意义。
