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局部晚期宫颈癌治疗前标本中PD-L1的表达及CD8阳性T细胞的存在情况。

Expression of PD-L1 and presence of CD8-positive T cells in pre-treatment specimens of locally advanced cervical cancer.

作者信息

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

机构信息

Translational Laboratories, Tom Baker Cancer Centre, Calgary, AB, Canada.

Department of Oncology, Tom Baker Cancer Centre, Calgary, AB, Canada.

出版信息

Mod Pathol. 2017 Apr;30(4):577-586. doi: 10.1038/modpathol.2016.221. Epub 2017 Jan 6.

Abstract

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.

摘要

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。

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