title: Epithelial PD-L2 Expression Marks Barrett's Esophagus and Esophageal Adenocarcinoma.
abstract: 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.
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Dept. of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sarah
authors.initials: S
authors.lastname: Derks
authors.affiliation: Dept. of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Katie S
authors.initials: KS
authors.lastname: Nason
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|The Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Liao
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Dept. of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Stachler
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Kevin X
authors.initials: KX
authors.lastname: Liu
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Jie Bin
authors.initials: JB
authors.lastname: Liu
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sicinska
authors.affiliation: Dept. of Cancer Immunology & AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Goldberg
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Dept. of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.affiliation: Dept. of Pathology, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Davison
authors.affiliation: Dept. of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.|Cancer Program, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. Boston, Massachusetts, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Bass
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism* / Q000473:pathology; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000235:genetics / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction; D047368:Tumor Burden
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; D018793:Interleukin-13; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D015847:Interleukin-4