Mukherji Deborah, Jabbour Mark N, Saroufim Maya, Temraz Sally, Nasr Rami, Charafeddine Maya, Assi Rita, Shamseddine Ali, Tawil Ayman N
Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center, Beirut, Lebanon.
Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon.
Clin Genitourin Cancer. 2016 Apr;14(2):183-7. doi: 10.1016/j.clgc.2015.12.002. Epub 2015 Dec 17.
The programmed death-1 (PD-1) pathway negatively regulates T-cell activation and has an important role in regulating antitumor host immunity. Monoclonal antibodies directed against PD-1 or the PD-1 ligand (PD-L1) have shown activity in several tumor types with preliminary data suggesting a relationship between PD-L1 expression and response. The aim of this study was to establish the frequency of PD-L1 expression in muscle-invasive bladder cancer and associated lymph node metastasis using immunohistochemistry and to investigate the feasibility of using PD-L1 expression as a biomarker to select patients for PD-1-directed therapy.
Cases of radical cystectomy for muscle-invasive bladder cancer with no exposure to previous chemotherapy were identified and representative slides from archived paraffin-embedded blocks stained with anti-PD-L1 antibody (5H1 clone) were identified. PD-L1 positivity was defined by a 5% expression threshold.
Fifty-two radical cystectomy specimens were reviewed. PD-L1 was overexpressed in the tumor cells of 5/52 (9.6%) of cystectomy specimens in this cohort with 17/52 (32.7%) of cases showing PD-L1 overexpression in tumor-infiltrating immune cells. Discordance was observed between PD-L1 expression in lymph node metastasis and the primary tumor.
Standard assays for PD-L1 expression have yet to be established. The observation of discordance between PD-L1 expression in metastatic sites and primary tumors suggests that prospective biomarker studies should aim to acquire material immediately before treatment initiation rather than archived tissue from resected specimens that might not reflect the current immune-active microenvironment.
程序性死亡蛋白1（PD-1）通路对T细胞活化起负调节作用，在调节抗肿瘤宿主免疫中发挥重要作用。针对PD-1或PD-1配体（PD-L1）的单克隆抗体已在多种肿瘤类型中显示出活性，初步数据表明PD-L1表达与反应之间存在关联。本研究的目的是通过免疫组织化学确定肌肉浸润性膀胱癌及相关淋巴结转移中PD-L1表达的频率，并研究将PD-L1表达用作生物标志物以选择接受PD-1导向治疗患者的可行性。
确定未接受过先前化疗的肌肉浸润性膀胱癌根治性膀胱切除术病例，并从存档的石蜡包埋块中找出用抗PD-L1抗体（5H1克隆）染色的代表性切片。PD-L1阳性定义为表达阈值为5%。
回顾了52例根治性膀胱切除术标本。在该队列中，5/52（9.6%）的膀胱切除术标本的肿瘤细胞中PD-L1过表达，17/52（32.7%）的病例在肿瘤浸润免疫细胞中显示PD-L1过表达。观察到淋巴结转移和原发性肿瘤中PD-L1表达不一致。
尚未建立PD-L1表达的标准检测方法。转移部位和原发性肿瘤中PD-L1表达不一致的观察结果表明，前瞻性生物标志物研究应旨在在治疗开始前立即获取材料，而不是从切除标本中获取可能无法反映当前免疫活性微环境的存档组织。
