Department of Oral and Maxillofacial Surgery, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Cancer Med. 2019 Mar;8(3):1124-1134. doi: 10.1002/cam4.1929. Epub 2019 Jan 18.
Despite the observed association of increased PD-L1 expression in peripheral blood of oral squamous cell carcinoma (OSCC) patients with histomorphologic parameters, the role of the PD1 ligands-PD-L1 and PD-L2-is insufficiently understood. Aim of the study was to investigate whether the alterations of PD-L1 and PD-L2 expression in blood are associated with survival and could serve as immune monitoring parameter. Moreover, it should be analyzed if PD-L2 is differentially expressed in tissue and blood samples of OSCC patients compared to healthy controls and if there is an association of PD-L2 expression with histomorphologic and prognostic tumor parameters.
PD-L2 mRNA expression was analyzed in tumors and healthy oral mucosa specimens and in corresponding peripheral blood samples of 48 OSCC patients and 26 healthy controls using RT-qPCR. A cutoff point (COP) was determined and a chi-square test (χ test) was carried out. Survival analysis of PD-L2 and previously reported PD-L1 expression data was performed using Kaplan-Meier analysis (Log-rank test).
PD-L2 expression in tissue samples was significantly (P < 0.001) higher in OSCC patients compared to healthy controls. A significant association of PD-L2 expression above the COP (positive) with malignancy was ascertained (P < 0.001). A significant (P = 0.01) association of previously reported PD-L1 expression rates in peripheral blood with survival could be shown.
Peripheral blood PD-L1 expression might be a prognostic marker for OSCC patients and a possible parameter to monitor immune dysfunction in malign diseases. In the peripheral blood, PD-L1 might be more relevant for immune tolerance than PD-L2. Local PD-L2 expression in tissue samples might be useful as a diagnostic parameter for malignancy and could contribute to the immunosuppressive local microenvironment in OSCC.
尽管观察到口腔鳞状细胞癌（OSCC）患者外周血中 PD-L1 表达增加与组织形态学参数有关，但 PD1 配体-PD-L1 和 PD-L2 的作用仍了解不足。本研究旨在探讨血液中 PD-L1 和 PD-L2 表达的改变是否与生存相关，并可作为免疫监测参数。此外，还应分析 PD-L2 在 OSCC 患者组织和血液样本中的表达是否与健康对照组存在差异，以及 PD-L2 表达是否与组织形态学和预后肿瘤参数相关。
使用 RT-qPCR 分析 48 例 OSCC 患者和 26 例健康对照者的肿瘤和健康口腔黏膜标本以及相应外周血样本中的 PD-L2 mRNA 表达。确定截断值（COP）并进行卡方检验（χ 检验）。使用 Kaplan-Meier 分析（Log-rank 检验）对 PD-L2 和先前报道的 PD-L1 表达数据进行生存分析。
组织样本中 PD-L2 的表达在 OSCC 患者中明显（P < 0.001）高于健康对照组。确定 COP 以上（阳性）PD-L2 表达与恶性肿瘤显著相关（P < 0.001）。先前报道的外周血 PD-L1 表达率与生存显著相关（P = 0.01）。
外周血 PD-L1 表达可能是 OSCC 患者的预后标志物，也是监测恶性疾病免疫功能障碍的可能参数。在外周血中，PD-L1 可能比 PD-L2 更与免疫耐受相关。组织样本中局部 PD-L2 表达可能是恶性肿瘤的有用诊断参数，并可能有助于 OSCC 局部免疫抑制微环境。
