Enwere Emeka K, Kornaga Elizabeth N, Dean Michelle, Koulis Theodora A, Phan Tien, Kalantarian Maria, Köbel Martin, Ghatage Prafull, Magliocco Anthony M, Lees-Miller Susan P, Doll Corinne M
Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.
Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.
Mod Pathol. 2017 Apr;30(4):577-586. doi: 10.1038/modpathol.2016.221. Epub 2017 Jan 6.
Several of the cancer immunotherapies under investigation or in clinical use target the programmed death-ligand 1/programmed death-1 (PD-L1/PD-1) signaling axis. PD-L1 expression in tumor samples has been used as a predictive marker for response to these therapeutics, and may also have independent prognostic utility when assessed along with immune cell markers. Our objectives were to assess the expression of PD-L1 in tumor specimens from a uniformly treated patient cohort with locally advanced cervical cancer, and to determine its prognostic significance along with the density of tumor-infiltrating T cells. We identified 120 patients with locally advanced cervical cancer treated with radical chemoradiotherapy, and built tissue microarrays from their formalin-fixed, paraffin-embedded pre-treatment biopsies. We used conventional brightfield and fluorescence immunohistochemistry to detect PD-L1, and quantified protein expression using both manual pathologist scoring and automated software analysis. We also evaluated the effect of PD-L1 expression in tumors, along with the presence and density of intra-tumoral CD8 T cells, on patient survival outcomes. Approximately 96% of the tumor samples expressed PD-L1, as determined using quantitative software analysis. Neither expression of PD-L1 nor density of CD8 T cells was associated with progression-free or overall survival. However, there was a trend towards worse progression-free survival in patients whose tumors expressed PD-L1 but lacked CD8 T cells (hazard ratio=0.43 (0.18-1.01), P=0.053). Nevertheless, the high percentage of cervical cancer tumor samples expressing PD-L1 suggests that anti-PD-L1 or anti-PD-1 therapies are potential treatment options for this patient population.
几种正在研究或临床使用的癌症免疫疗法靶向程序性死亡配体1/程序性死亡1（PD-L1/PD-1）信号轴。肿瘤样本中的PD-L1表达已被用作这些疗法反应的预测标志物，并且在与免疫细胞标志物一起评估时也可能具有独立的预后价值。我们的目标是评估局部晚期宫颈癌统一治疗患者队列肿瘤标本中PD-L1的表达，并确定其与肿瘤浸润性T细胞密度的预后意义。我们确定了120例接受根治性放化疗的局部晚期宫颈癌患者，并从他们的福尔马林固定、石蜡包埋的治疗前活检组织中构建组织微阵列。我们使用传统的明场和荧光免疫组织化学检测PD-L1，并使用病理学家手动评分和自动化软件分析对蛋白表达进行定量。我们还评估了肿瘤中PD-L1表达以及肿瘤内CD8 T细胞的存在和密度对患者生存结果的影响。使用定量软件分析确定，约96%的肿瘤样本表达PD-L1。PD-L1的表达和CD8 T细胞的密度均与无进展生存期或总生存期无关。然而，肿瘤表达PD-L1但缺乏CD8 T细胞的患者无进展生存期有变差的趋势（风险比=0.43（0.18-1.01），P=0.053）。尽管如此，宫颈癌肿瘤样本中高比例表达PD-L1表明抗PD-L1或抗PD-1疗法是该患者群体的潜在治疗选择。
