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

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-a are discussed, with a particular focus on perioperative stimulation of immune function in cancer patients. IFN-a 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-a 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-a enhanced activation markers on T cells and NK cells, combined with betterpreserved 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-a 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.