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Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus
Authors:Marinke Westerterp  Marja A Boermeester  Jikke M T Omloo  Maarten C C M Hulshof  Walter L Vervenne  Rene Lutter  Theo A Out  J Jan B van Lanschot
Institution:(1) Department of Surgery, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;(2) Department of Radiotherapy, Academic Medical Centre, Amsterdam, The Netherlands;(3) Department of Medical Oncology, Academic Medical Centre, Amsterdam, The Netherlands;(4) Department of Experimental Immunology, Academic Medical Centre, Amsterdam, The Netherlands;(5) Department of Pulmonology, Academic Medical Centre, Amsterdam, The Netherlands
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. Conclusion  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.
Keywords:Oesophageal cancer  Neoadjuvant therapy  Surgery  Immune response  T cell imbalance
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