The University of Virginia, Department of Pathology, Charlottesville, VA.
The University of Virginia, Department of Pathology, Charlottesville, VA.
Hum Pathol. 2018 Nov;81:184-191. doi: 10.1016/j.humpath.2018.06.028. Epub 2018 Jun 30.
Programmed death ligand 1 (PD-L1) is a transmembrane protein that plays a major role in immune suppression. Its interaction with the receptor PD-1 results in downregulation of antitumoral immunity. Humanized monoclonal antibodies that interrupt the PD-L1/PD-1 interaction have shown therapeutic efficacy in patients with advanced urothelial cancer. However, immunohistochemical staining of PD-L1 in bladder tumors and its relationship to tumor histologic type, grade, and overall survival has been incompletely analyzed. Slides from 165 cystectomy specimens were reviewed for tumor type, grade of urothelial carcinoma, pathologic stage, and overall survival. A tissue microarray (TMA) using four 0.6 mm cores from each case was constructed. Immunohistochemistry was performed on the TMA using a variety of new PD-L1 antibodies and platforms now widely available. For each case, the percent of tumor cells positive for PD-L1 and the percent of positive immune cells were scored. The overall number of bladder cancers positive for PD-L1 depended on the antibody/platform combination used and the threshold for considering a tumor "PD-L1-positive." Squamous cell carcinomas (SCCs) of the bladder demonstrated PD-L1 positivity more frequently than urothelial cell carcinomas (UCCs). High-grade UCCs were positive for PD-L1 on tumor cells more frequently than low-grade UCCs. There was no difference in survival between PD-L1-positive and PD-L1-negative bladder cancers in our study. Further studies should consider examining the predictive significance of PD-L1 IHC in bladder cancers.
程序性死亡配体 1（PD-L1）是一种跨膜蛋白，在免疫抑制中起主要作用。它与受体 PD-1 的相互作用导致抗肿瘤免疫的下调。阻断 PD-L1/PD-1 相互作用的人源化单克隆抗体已在晚期尿路上皮癌患者中显示出治疗疗效。然而，膀胱肿瘤中 PD-L1 的免疫组织化学染色及其与肿瘤组织学类型、分级和总生存的关系尚未得到充分分析。对 165 例膀胱切除术标本的切片进行了肿瘤类型、尿路上皮癌分级、病理分期和总生存的回顾。使用每个病例的 4 个 0.6 毫米核心构建了组织微阵列（TMA）。使用现在广泛可用的各种新的 PD-L1 抗体和平台对 TMA 进行免疫组织化学染色。对于每个病例，对 PD-L1 阳性的肿瘤细胞百分比和阳性免疫细胞的百分比进行评分。膀胱癌中 PD-L1 阳性的总数取决于所使用的抗体/平台组合以及考虑肿瘤“PD-L1 阳性”的阈值。膀胱鳞状细胞癌（SCC）比尿路上皮细胞癌（UCC）更常表现出 PD-L1 阳性。高级别 UCC 肿瘤细胞中 PD-L1 的阳性率高于低级别 UCC。在我们的研究中，PD-L1 阳性和 PD-L1 阴性膀胱癌之间的生存没有差异。进一步的研究应考虑检查 PD-L1 IHC 在膀胱癌中的预测意义。
