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

• Autores: S.J. Oosterling, G. J. Van der Bij, A. K. Mels, R.H.J. Beelen, S. Meijer, M. van Egmond, P.A.M. van Leeuwen
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 21, Nº. 7, 2006, págs. 753-760
• Idioma: inglés
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  • Summary. 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