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

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.