title: Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus.
abstract: BACKGROUND
  To compare immune responses following neoadjuvant chemoradiation therapy in combination with hyperthermia plus surgery to those induced by surgery alone in patients with oesophageal cancer.
  
  
  METHODS
  Thirty-two patients with histopathologically proven oesophageal cancer, scheduled for potentially curative transhiatal or transthoracic oesophagectomy with (neo, n = 20) or without (control, n = 12) neoadjuvant thermochemoradiation therapy (ThCR) were included. Peripheral blood samples were obtained before ThCR, after 2 weeks of ThCR, 1 day before surgery, on postoperative days 1, 3, 7, and 6 weeks after surgery, for white blood cell counts, lymphocyte subsets and T helper type 1 (Th1) and type 2 (Th2) lymphocyte responses.
  
  
  RESULTS
  Neo patients showed a significant decrease in granulocytes and lymphocyte subsets, and T cell cytokines after 2 weeks of ThCR. Only CD8+ (cytotoxic) T cells recovered after ThCR to reach normal levels prior to surgery. In contrast, CD4+ T (helper) cells, and NK- and B cells in neo patients did not recover prior to surgery (all P < 0.05). Oesophagectomy induced a significant increase in granulocytes and a decrease in lymphocytes (and subsets). Only those subsets that had not recovered after ThCR (CD4+ T cells, NK and B cells but not CD8+ T cells), were significantly lower (all P < 0.05) during the entire postoperative study period. Postoperatively, the stimulated cytokine production capacity of Th1 and Th2 cells, corrected for number of T cells, was not significantly different between the groups.
  
  
  CONCLUSIONS
  Neoadjuvant thermochemoradiation for oesophageal cancer caused significant disturbances of host cellular immunity with reduced T, NK and B cell counts, and differential recovery of cytotoxic and helper T cells leading to prolonged T cell imbalance that extends beyond the time of surgery. The functional and anti-tumour consequences of this immunodisturbance need further investigation, as recovery of T helper cytokine production towards surgery was less impaired than T helper cell counts.
authors.affiliation: Department of Surgery, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. mwesterterp@hotmail.com
authors.forename: Marinke
authors.initials: M
authors.lastname: Westerterp
authors.forename: Marja A
authors.initials: MA
authors.lastname: Boermeester
authors.forename: Jikke M T
authors.initials: JM
authors.lastname: Omloo
authors.forename: Maarten C C M
authors.initials: MC
authors.lastname: Hulshof
authors.forename: Walter L
authors.initials: WL
authors.lastname: Vervenne
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.forename: Theo A
authors.initials: TA
authors.lastname: Out
authors.forename: J Jan B
authors.initials: JJ
authors.lastname: van Lanschot
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000528:radiation effects; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011878:Radiotherapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000528:radiation effects; D018417:Th1 Cells / Q000187:drug effects / Q000528:radiation effects; D018418:Th2 Cells / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents