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Lymphocyte subsets and T(h)1/T(h)2 immune responses in patients with adenocarcinoma of the oesophagus or oesophagogastric junction: relation to pTNM stage and clinical outcome
Authors:van Sandick Johanna W  Boermeester Marja A  Gisbertz Suzanne S  ten Berge Ineke J M  Out Theo A  van der Pouw Kraan Tineke C T M  van Lanschot J Jan B
Institution:(1) Department of Surgery, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;(2) Department of Internal Medicine 2, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;(3) Department of Clinical and Laboratory Immunology Unit, Academic Medical Center, Amsterdam, The Netherlands;(4) Central Laboratory, The Netherlands Red Cross Blood Transfusion Service, The Netherlands
Abstract:Introduction Recent studies have indicated that the cytokines produced by CD4+ T helper type 1 (Th1) and type 2 (Th2) cells are critically important in antitumour immunity and perhaps clinical outcome. From this perspective, we investigated the immunocompetence of patients with previously untreated cancer of the oesophagus or oesophagogastric junction (OGJ) in relation to stage of disease and postoperative survival.Methods Blood samples were taken prior to surgery from 32 patients with adenocarcinoma of the oesophagus or OGJ. Ten healthy volunteers served as normal controls. T-cell and monocyte subpopulations were determined using flow cytometry. Monocyte as well as Th1- and Th2-lymphocyte cytokine levels were assessed in stimulated whole blood cultures.Results Absolute T-cell and monocyte (subset) counts as well as monocyte cytokine levels were similar among patients and controls. Production of Th1-type cytokines was higher in patients than in controls (IFN-gamma, p=0.01; IL-2, p=0.05), whereas Th2-type cytokine levels were comparable (IL-4, p=0.5; IL-13, p=0.3). T-cell CD4+/CD8+ ratios decreased as pTNM stage worsened (stage I/II vs stage III/IV, p=0.009). Of all measured immunological parameters, only IL-2 production significantly affected both overall survival (p=0.015) and disease-free survival (p=0.0062). High IL-2 levels corresponded with a favourable prognosis.Conclusions Patients awaiting surgery for adenocarcinoma of the oesophagus or oesophagogastric junction demonstrated a shift in the Th1/Th2 balance—in favour of Th1—compared with healthy volunteers. The ability of T cells to produce IL-2 was related to survival indicating a crucial role of Th1-type cells in antitumour immunosurveillance.
Keywords:Cytokines  Oesophagus  Prognosis  Surgery  h1/Th2" target="_blank">Th1/Th2
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