title: Dendritic cells in Barrett's esophagus carcinogenesis: an inadequate microenvironment for antitumor immunity?
abstract: Barrett's esophagus corresponds to the replacement of the normal esophageal squamous epithelium by a columnar epithelium through a metaplastic process. This tissue remodeling is associated with chronic gastroesophageal reflux and constitutes a premalignant lesion leading to a 30- to 60-fold increase in the risk to evolve into esophageal adenocarcinoma. The present study aimed to investigate a possible immune evasion in Barrett's esophagus favoring esophageal adenocarcinoma development. We demonstrated that myeloid and plasmacytoid dendritic cells are recruited during the esophageal metaplasia-dysplasia-carcinoma sequence, through the action of their chemoattractants, macrophage inflammatory protein 3α and chemerin. Next, we showed that, in contrast to plasmacytoid dendritic cells, myeloid dendritic cells, co-cultured with Barrett's esophagus and esophageal adenocarcinoma cell lines, display a tolerogenic phenotype. Accordingly, myeloid dendritic cells co-cultured with esophageal adenocarcinoma cell lines stimulated regulatory T cell differentiation from naïve CD4(+) T cells. In agreement with those results, we observed that both metaplastic areas and (pre)malignant lesions of the esophagus are infiltrated by regulatory T cells. In conclusion, soluble factors secreted by epithelial cells during the esophageal metaplasia-dysplasia-carcinoma sequence influence dendritic cell distribution and promote tumor progression by rendering them tolerogenic.
authors.affiliation: Department of Pathology, University Hospital of Liege, Liege, Belgium.
authors.forename: Joan
authors.initials: J
authors.lastname: Somja
authors.forename: Stephanie
authors.initials: S
authors.lastname: Demoulin
authors.forename: Patrick
authors.initials: P
authors.lastname: Roncarati
authors.forename: Michaël
authors.initials: M
authors.lastname: Herfs
authors.forename: Noella
authors.initials: N
authors.lastname: Bletard
authors.forename: Philippe
authors.initials: P
authors.lastname: Delvenne
authors.forename: Pascale
authors.initials: P
authors.lastname: Hubert
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D054418:Chemokine CCL20 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000276:immunology*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000276:immunology*; D053245:RANK Ligand / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D053245:RANK Ligand; C478630:RARRES2 protein, human; C505688:TNFSF11 protein, human