Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus

• Published in: Cancer Immunology, Immunotherapy Vol. 57; no. 12; pp. 1837 - 1847
• Main Authors: Westerterp, Marinke, Boermeester, Marja A., Omloo, Jikke M. T., Hulshof, Maarten C. C. M., Vervenne, Walter L., Lutter, Rene, Out, Theo A., van Lanschot, J. Jan B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2008; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - administration & dosage; B-Lymphocytes - drug effects; B-Lymphocytes - radiation effects; Biological and medical sciences; Cancer Research; Combined Modality Therapy; Esophageal Neoplasms - immunology; Esophageal Neoplasms - therapy; Esophagectomy; Esophagus; Female; Gastroenterology. Liver. Pancreas. Abdomen; Granulocytes - drug effects; Granulocytes - radiation effects; Humans; Immunology; Immunotherapy; Killer Cells, Natural - drug effects; Killer Cells, Natural - radiation effects; Leukocyte Count; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoadjuvant Therapy; Oncology; Original; Original Article; Pharmacology. Drug treatments; Radiotherapy; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - radiation effects; Th1 Cells - drug effects; Th1 Cells - radiation effects; Th2 Cells - drug effects; Th2 Cells - radiation effects; Tumors; T cell imbalance; Oesophageal cancer; Neoadjuvant therapy; Immune response; Surgery; Human; Carcinoma; Digestive system; Esophageal disease; Patient; Cellular immunity; Malignant tumor; Esophagus cancer; Neoadjuvant treatment; Esophagus; Immunotherapy; T-Lymphocyte; Digestive diseases; Oesophageal cancer; Neoadjuvant therapy· Surgery; Immune response; T cell imbalance; Cancer
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-008-0511-8

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.