Differential responses of cellular immunity in patients undergoing neoadjuvant therapy followed by surgery for carcinoma of the oesophagus.
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.
Westerterp
Marinke
M
Department of Surgery, Academic Medical Centre, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. mwesterterp@hotmail.com
Boermeester
Marja A
MA
Omloo
Jikke M T
JM
Hulshof
Maarten C C M
MC
Vervenne
Walter L
WL
Lutter
Rene
R
Out
Theo A
TA
van Lanschot
J Jan B
JJ
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
D000970:Antineoplastic Agents