Peri-operative modulation of cellular immunity in patients with colorectal cancer.
The peri-operative cellular immune response is depressed in patients with gastrointestinal cancer, a factor which may facilitate malignant dissemination. We have investigated the effects of peri-operative rIL-2 and a combination of rIL-2 and interferon-alpha (IFN-alpha) 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-alpha treatment arms. In vitro studies were performed pre-operatively and on post-operative days 1, 4, 7 and 10. Natural killer (NK) and lymphokine-activated killer (LAK) cell function were profoundly depressed in control patients (P < 0.001; P < 0.01), an effect abrogated in both treatment groups; indeed NK function was augmented in the rIL-2 and IFN-alpha 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-alpha 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.
Nichols
P H
PH
Academic Unit of Surgery, St James's University Hospital, Leeds, UK.
Ramsden
C W
CW
Ward
U
U
Trejdosiewicz
L K
LK
Ambrose
N S
NS
Primrose
J N
JN
D015179:Colorectal Neoplasms / Q000276:immunology* / Q000601:surgery / Q000628:therapy; D003131:Combined Modality Therapy; D006801:Humans; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007370:Interferon Type I / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000096:biosynthesis / Q000627:therapeutic use*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D011184:Postoperative Period; D011292:Premedication; D011994:Recombinant Proteins / Q000627:therapeutic use
D007370:Interferon Type I; D007376:Interleukin-2; D011994:Recombinant Proteins