Kollmann Dagmar, Ignatova Desislava, Jedamzik Julia, Chang Yun-Tsan, Jomrich Gerd, Baierl Andreas, Kazakov Dmitry, Michal Michal, French Lars E, Hoetzenecker Wolfram, Schatton Tobias, Asari Reza, Preusser Matthias, Gnant Michael, Guenova Emmanuella, Schoppmann Sebastian F
Department of Surgery and Comprehensive Cancer Center, GET-Unit, Medical University of Vienna, Vienna, Austria.
Department of Dermatology, University Hospital Zürich, University of Zurich, Zurich, Switzerland.
Oncoimmunology. 2018 Mar 13;7(6):e1435226. doi: 10.1080/2162402X.2018.1435226. eCollection 2018.
. The outcome of patients with adenocarcinoma of the esophagogastric junction (AEG) remains poor. The programmed cell-death-protein-1 (PD-1), a co-inhibitory receptor primarily expressed by T-cells, represents a potential new therapeutic target. PD-1, PD-1 ligand 1 (PD-L1), and PD-L2 expression have all been described as prognostic factors in a variety of cancers. Their expression patterns in AEG, however, are poorly understood. We analyzed PD-L1, PD-L2 and PD-1 expression by tumor-infiltrating lymphocytes (TILs) and cancer-cells in tumor-biospecimens in AEG-patients. . 168 patients who underwent esophagectomy because of AEG between 1992-2011 were included in this study. PD-L1, PD-L2 and PD-1 expression were evaluated by immunohistochemistry and correlated with various clinicopathological parameters, disease-free survival (DFS) and long-term overall survival (OS). . PD-L1 expression by cancer-cells (cancer-cell-PD-L1) was found in 43.5% of patients whereas PD-L1 expression by TILs (TILs-PD-L1) was observed in 69%. PD-L2 expression by cancer-cells and TILs was only found in 3.5% and 1.8%, respectively. Additionally, 77.4% of tumors contained PD-1-cancer-cells and 81% PD-1-TILs. Patients with increased expression of PD-1 by cancer-cells and TILs showed significantly reduced OS and DFS, as determined by univariate, but not multivariate analysis. Expression of PD-L1 by cancer-cells was found to be an independent predictor for improved DFS (p = 0.038) and OS (p = 0.042) in multivariate analysis. . Cancer cells and TILs displayed PD-L1 expression in around 50% and PD-1 expression in around 80% of tumor-biospecimens obtained from AEG patients. Expression of PD-L1 is an independent predictor of favorable outcome in AEG, whereas PD-1 expression is associated with worse outcome and advanced tumor stage.
食管胃交界腺癌(AEG)患者的预后仍然很差。程序性细胞死亡蛋白1(PD-1)是一种主要由T细胞表达的共抑制受体,是一个潜在的新治疗靶点。PD-1、PD-1配体1(PD-L1)和PD-L2的表达均已被描述为多种癌症的预后因素。然而,它们在AEG中的表达模式却知之甚少。我们分析了AEG患者肿瘤生物标本中肿瘤浸润淋巴细胞(TILs)和癌细胞的PD-L1、PD-L2和PD-1表达情况。本研究纳入了1992年至2011年间因AEG接受食管切除术的168例患者。通过免疫组织化学评估PD-L1、PD-L2和PD-1的表达,并将其与各种临床病理参数、无病生存期(DFS)和长期总生存期(OS)相关联。43.5%的患者癌细胞有PD-L1表达(癌细胞-PD-L1),而69%的患者TILs有PD-L1表达(TILs-PD-L1)。癌细胞和TILs的PD-L2表达分别仅在3.5%和1.8%的患者中发现。此外,77.4%的肿瘤含有PD-1阳性癌细胞,81%含有PD-1阳性TILs。单因素分析显示,癌细胞和TILs中PD-1表达增加的患者OS和DFS显著降低,但多因素分析未显示。多因素分析发现,癌细胞PD-L1表达是DFS改善(p = 0.038)和OS改善(p = 0.042)的独立预测因素。在从AEG患者获得的约50%的肿瘤生物标本中,癌细胞和TILs显示有PD-L1表达,约80%显示有PD-1表达。PD-L1表达是AEG患者预后良好的独立预测因素,而PD-1表达与较差的预后和晚期肿瘤分期相关。