Peri-operative modulation of cellular immunity in patients with colorectal cancer

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Abstract
SUMMARY: The peri-operalive cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate maligtiant dissemination. We have investigated the effects of perioperative rIL-2 and a combination of rlL-2 and interferon-alpha (IFN-α) on both peripheral blood lymphocyte function and number in patients undergoing surgical resection for colorectal cancer. Fifty-two patients were randomly allocated to either control, rIL-2 or rIL-2 with IFN-α treatment arms. In vitro studies were performed pre-operatively and on post-operative days I, 4, 7 and 10. Natural ikller (NK) and lymphokine-activated killer (LAK) cell function were profoundly depressed in control patients (P < 0·001; P < 0·001), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL-2 and IFN-α group on the first post-operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cytometric analysis of lymphocyte subsets in the control group was unremarkable, except for an early post-operative fall in numbers of lymphocytes. Treatment with either rIL-2 or rIL-2 and IFN-α produced an initial profound reduction in T lymphocyte numbers, followed by a ‘rebound’ lymphocytosis of activated CD3+ T cells, as demonstrated by a significant increase in co-expression of CD25, CD38, and CD45RO. No significant differences were observed between either of the treatment groups. Adjuvant immunotherapy affects peri-operative anti-tumour immune responses, and this may influence long term outcome in patients undergoing surgery for gastrointestinal cancer.