Perioperative IFN-alpha to avoid surgically induced immune suppression in colorectal cancer patients

Histol Histopathol. 2006 Jul;21(7):753-60. doi: 10.14670/HH-21.753.

Abstract

Surgical treatment of colorectal cancer is associated with postoperative immunosuppression, which might facilitate dissemination of tumor cells and outgrowth of minimal residual disease/(micro) metastases. Minimal residual disease has been shown to be of prognostic relevance in colorectal cancer. Therefore, stimulation of (anti-tumor) immune responses may be beneficial in the prevention of metastases formation. Important anti-tumor effector cells, which serve this function, are natural killer (NK) cells, CD8+ lymphocytes (CTL), dendritic cells (DC) and macrophages. In this review the immunomodulating properties of IFN-alpha are discussed, with a particular focus on perioperative stimulation of immune function in cancer patients. IFN-alpha is known to enhance innate immune functions such as stimulation of NK cells, transition from innate to adaptive responses (activation of DC) and regulating of CD8+ CTL activity and memory. Moreover, it exerts direct antitumor effects by regulating apoptosis and cell cycle. In several clinical trials, perioperative administration of IFN-alpha has indeed been shown to improve T cell responsiveness, prevent impairment of NK cell cytotoxicity and increase expression of activation markers on NK, T and NKT cells. In a clinical pilot study we showed in colorectal cancer patients that received perioperative IFN-alpha enhanced activation markers on T cells and NK cells, combined with better-preserved T cell function as indicated by phytohemaggluttinin skin tests. In the liver of these patients significantly more CD8+ T cells were found. In conclusion, IFN-alpha provides an effective adjuvant in several forms of cancer and improves several postoperative immune functions in perioperative administration. However, larger clinical trials are necessary to investigate effects on disease-free and overall survival.

Publication types

  • Review

MeSH terms

  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / immunology*
  • Colorectal Neoplasms / surgery
  • Humans
  • Immunologic Factors / therapeutic use*
  • Immunosuppression*
  • Interferon-alpha / therapeutic use*
  • Perioperative Care*
  • Postoperative Complications* / immunology
  • Postoperative Complications* / prevention & control

Substances

  • Immunologic Factors
  • Interferon-alpha