PERIOPERATIVE MODULATION OF CELLULAR-IMMUNITY IN PATIENTS WITH COLORECTAL-CANCER

The peri-operative cellular immune response is depressed in patients w ith gastrointestinal cancer, a factor which may facilitate malignant d issemination. We have investigated the effects of peri-operative rIL-2 and a combination of rIL-2 and interferon-alpha (IFN-alpha on both pe ripheral blood lymphocyte function and number in patients undergoing s urgical resection for colorectal cancer. Fifty-two patients were rando mly allocated to either control, rIL-2 or rIL-2 with IFN-alpha treatme nt arms. In vitro studies were performed pre-operatively and on post-o perative days 1, 4, 7 and 10. Natural killer (NK) and lymphokine-activ ated killer (LAK) cell function were profoundly depressed in control p atients (P < 0.001; P < 0.01), an effect abrogated in both treatment g roups; indeed NK function was augmented in the rIL-2 and IFN-alpha gro up on the first post-operative day in association with an increase in the percentage of cells expressing CD16 and CD56 (P < 0.01). Flow cyto metric analysis of lymphocyte subsets in the control group was unremar kable, except for an early postoperative fall in numbers of lymphocyte s. Treatment with either rIL-2 or rIL-2 and IFN-alpha produced an init ial profound reduction in T lymphocyte numbers, followed by a 'rebound ' lymphocytosis of activated CD3+ T cells, as demonstrated by a signif icant increase in co-expression of CD25, CD38 and CD45RO. No significa nt differences were observed between either of the treatment groups. A djuvant immunotherapy affects peri-operative anti-tumour immune respon ses, and this may influence long term outcome in patients undergoing s urgery for gastrointestinal cancer.