title: Impact of the inflammatory microenvironment on T-cell phenotype in the progression from reflux oesophagitis to Barrett oesophagus and oesophageal adenocarcinoma.
abstract: The incidence of oesophageal adenocarcinoma (OAC), arising from reflux-induced Barrett oesophagus (BO), is increasing dramatically. T-cells have recently been implicated in the initiation of oesophagitis; however, their role in the progression from oesophagitis to BO and OAC has not been fully elucidated. Previous studies have examined the secreted cytokines from oesophageal tissue during disease progression but this study is the first to examine the activation phenotype and the inflammatory profile of CD4(+) and CD8(+) T-cells in human oesophagitis, BO and OAC tissue. Results demonstrated significantly higher levels of IL-4 producing CD4(+) T-cells and secreted levels of IL-6, confirming a Th2 phenotype in BO. In OAC tissue, both pro- and anti-inflammatory cytokines were secreted, with significantly higher levels of IL-6, IL-1β, TNF-α, IFN-γ, IL-2 and IL-10 compared with normal oesophageal tissue. In addition, CD4(+) T-cells infiltrating OAC tissue displayed a decreased activation profile, with significantly lower CD45RO and CD69 expression compared with normal tissue. Data from this study suggest that factors in the tissue microenvironment may alter T-cell phenotype and function early during oesophageal disease progression and may represent targets for immune intervention.
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Kavanagh
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Conroy
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Niamh E
authors.initials: NE
authors.lastname: Clarke
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Niamh T
authors.initials: NT
authors.lastname: Gilmartin
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Katie E
authors.initials: KE
authors.lastname: O'Sullivan
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Ronan
authors.initials: R
authors.lastname: Feighery
authors.affiliation: Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Finbar
authors.initials: F
authors.lastname: MacCarthy
authors.affiliation: Department of Clinical Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Dermot
authors.initials: D
authors.lastname: O'Toole
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Narayanasamy
authors.initials: N
authors.lastname: Ravi
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: John V
authors.initials: JV
authors.lastname: Reynolds
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Jacintha
authors.initials: J
authors.lastname: O'Sullivan
authors.affiliation: Department of Surgery, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland. Electronic address: jlysaght@tcd.ie.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lysaght
mesh_terms: D000230:Adenocarcinoma / Q000209:etiology* / Q000276:immunology; D001471:Barrett Esophagus / Q000209:etiology* / Q000276:immunology; D060833:Cellular Microenvironment; D016207:Cytokines / Q000032:analysis / Q000502:physiology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000209:etiology* / Q000276:immunology; D004942:Esophagitis, Peptic / Q000150:complications* / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines
keywords: Barrett oesophagus; Inflammation; Oesophageal adenocarcinoma; Oesophagitis; T-cells