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

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Perioperative IFNa to avoid surgically induced immune suppression.pdf(4.48 MB)
Date
2006
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Authors
Oosterling, S.J. ; van der Bij, G.J. ; Mels, A.K. ; Beelen, R.H.J. ; Meijer, S. ; van Egmond, M. ; van Leeuwen, P.A.M.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
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.
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Surgery , Colorectal cancer
Citation
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http://hdl.handle.net/10201/22674
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Histology and histopathology Vol.21, nº 7 (2006)
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