PD-L1 expression is an independent predictor of favorable outcome in patients with localized esophageal adenocarcinoma. (3rd June 2018)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Oncoimmunology. Volume 7:Number 6(2018)
• Publication Date: 2018-06-03
• Subjects: PD-1 -- PD-L1 -- PD-L2 -- esophageal adenocarcinoma -- esophageal carcinoma; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1435226
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Background . 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. Methods . 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). Results . 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. Conclusions . 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.