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

Clin Exp Immunol. 1993 Oct;94(1):4-10. doi: 10.1111/j.1365-2249.1993.tb05968.x.

Abstract

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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / surgery
  • Colorectal Neoplasms / therapy
  • Combined Modality Therapy
  • Humans
  • Immunity, Cellular
  • Immunophenotyping
  • Interferon Type I / therapeutic use*
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / therapeutic use*
  • Killer Cells, Lymphokine-Activated / immunology
  • Killer Cells, Natural / immunology
  • Lymphocyte Activation
  • Postoperative Period
  • Premedication
  • Recombinant Proteins / therapeutic use

Substances

  • Interferon Type I
  • Interleukin-2
  • Recombinant Proteins