Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma

• Published in: Cancer immunology research Vol. 3; no. 10; p. 1123
• Main Authors: Derks, Sarah, Nason, Katie S, Liao, Xiaoyun, Stachler, Matthew D, Liu, Kevin X, Liu, Jie Bin, Sicinska, Ewa, Goldberg, Michael S, Freeman, Gordon J, Rodig, Scott J, Davison, Jon M, Bass, Adam J
• Format: Journal Article
• Language: English
• Published: United States 01.10.2015
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Aged; Animals; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Barrett Esophagus - genetics; Barrett Esophagus - metabolism; Barrett Esophagus - pathology; Biomarkers; Cell Line, Tumor; Disease Models, Animal; Disease Progression; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Female; Gene Expression; Heterografts; Humans; Immunohistochemistry; Interleukin-13 - metabolism; Interleukin-4 - metabolism; Male; Mice; Middle Aged; Mucous Membrane - metabolism; Mucous Membrane - pathology; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Programmed Cell Death 1 Ligand 2 Protein - genetics; Programmed Cell Death 1 Ligand 2 Protein - metabolism; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Reproducibility of Results; Signal Transduction; Tumor Burden
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.CIR-15-0046

Esophageal adenocarcinoma is an increasingly common disease with a dismal 5-year survival rate of 10% to 15%. In the first systematic evaluation of the PD-1 pathway in esophageal adenocarcinoma, we identify expression of PD-L2 in cancer cells in 51.7% of esophageal adenocarcinomas. Epithelial PD-L1 was expressed on only 2% of cases, although PD-L1(+) immune cells were observed in 18% of esophageal adenocarcinomas. We also evaluated expression in the precursor lesion of esophageal adenocarcinoma, Barrett's esophagus, which emerges following gastric reflux-induced esophageal inflammation, and found PD-L2 expression in Barrett's esophagus but not in non-Barrett's esophagus esophagitis. Because the progression from squamous esophagitis to Barrett's esophagus is accompanied by a transition from a TH1 to TH2 immune response, we hypothesized that the TH2 cytokines IL4/IL13 could contribute to PD-L2 induction. We confirmed that these cytokines can augment PD-L2 expression in esophageal adenocarcinoma cell lines. These results suggest that the inflammatory environment in Barrett's esophagus and esophageal adenocarcinoma may contribute to the expression of PD-L2. Furthermore, the potential for PD-1 receptor blockade to be effective in esophageal adenocarcinomas with epithelial PD-L2 or immune cell PD-L1 expression should be evaluated in clinical trials.