Bladder Cancer Center, Dana-Farber Cancer Institute, Boston; Medical Oncology Department, Brigham and Women's Hospital, Boston; Medical Oncology Department, Harvard Medical School, Boston; Medical Oncology Department, Dana-Farber Cancer Institute, Boston.
Bladder Cancer Center, Dana-Farber Cancer Institute, Boston; Medical Oncology Department, Dana-Farber Cancer Institute, Boston.
Ann Oncol. 2015 Apr;26(4):812-817. doi: 10.1093/annonc/mdv009. Epub 2015 Jan 18.
Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway negatively regulates T-cell-mediated responses. The prognostic impact of PD-L1 expression needs to be defined in urothelial carcinoma (UC).
Formalin-fixed paraffin-embedded tumor samples from 160 patients with UC were retrieved. PD-L1 expression was evaluated by immunohistochemistry using a mouse monoclonal anti-PD-L1 antibody (405.9A11). PD-L1 positivity on tumor cell membrane was defined as ≥5% of tumor cell membrane staining. The extent of tumor-infiltrating mononuclear cells (TIMCs) as well as PD-L1 expression on TIMCs was scored from 0 to 4. A score of 2, 3, or 4 was considered PD-L1-positive. Clinico-pathological variables were documented. The Cox regression model was used to assess the association of PD-L1 expression with overall survival (OS) in patients who developed metastases.
TIMCs were present in 143 of the 160 patient samples. Out of 160 samples, 32 (20%) had positive PD-L1 expression in tumor cell membrane. Out of 143 samples with TIMCs, 58 (40%) had positive PD-L1 expression in TIMCs. Smoking history, prior BCG use and chromosome 9 loss did not correlate with PD-L1 expression in either tumor cell membrane or TIMCs. PD-L1 positivity was not different between non-invasive or invasive UC. In patients who developed metastases (M1) and were treated with systemic therapy (n = 100), PD-L1 positivity on tumor cell membrane was seen in 14% of patients and did not correlate with OS (P = 0.45). Out of 89 M1 patients who had evaluable PD-L1 on TIMCs, PD-L1 expression was seen in 33% of patients and was significantly associated with longer OS on multivariate analysis (P = 0.0007).
PD-L1 is widely expressed in tumor cell membrane and TIMCs in UC. PD-L1 in tumor cells was not predictive of OS. However, positive PD-L1 expression in TIMCs was significantly associated with longer survival in those patients who developed metastases.
程序性死亡受体-1（PD-1）/PD-1 配体（PD-L1）通路负性调节 T 细胞介导的反应。PD-L1 表达的预后影响需要在尿路上皮癌（UC）中确定。
从 160 例 UC 患者中获取福尔马林固定石蜡包埋的肿瘤标本。使用鼠单克隆抗 PD-L1 抗体（405.9A11）通过免疫组织化学评估 PD-L1 表达。肿瘤细胞膜上的 PD-L1 阳性定义为≥5%的肿瘤细胞膜染色。肿瘤浸润单核细胞（TIMC）的程度以及 TIMC 上的 PD-L1 表达均评分为 0 至 4 分。评分 2、3 或 4 被认为是 PD-L1 阳性。记录临床病理变量。Cox 回归模型用于评估 PD-L1 表达与发生转移的患者总生存（OS）的相关性。
在 160 例患者样本中有 143 例存在 TIMC。在 160 例样本中，32 例（20%）肿瘤细胞膜上存在 PD-L1 阳性表达。在有 TIMC 的 143 例样本中，58 例（40%）TIMC 上存在 PD-L1 阳性表达。吸烟史、卡介苗（BCG）既往使用和 9 号染色体缺失与肿瘤细胞膜或 TIMC 中的 PD-L1 表达均无相关性。非浸润性或浸润性 UC 之间 PD-L1 阳性率无差异。在发生转移（M1）并接受系统治疗（n = 100）的患者中，肿瘤细胞膜上的 PD-L1 阳性率为 14%，与 OS 无相关性（P = 0.45）。在 89 例可评估 TIMC 上 PD-L1 的 M1 患者中，33%的患者 PD-L1 表达阳性，多变量分析显示其与更长的 OS 显著相关（P = 0.0007）。
PD-L1 在 UC 的肿瘤细胞膜和 TIMC 中广泛表达。肿瘤细胞中的 PD-L1 与 OS 无关。然而，在发生转移的患者中，TIMC 上的阳性 PD-L1 表达与更长的生存时间显著相关。
