title: Perioperative IFN-alpha 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-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.
authors.affiliation: Department of Surgical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: S J
authors.initials: SJ
authors.lastname: Oosterling
authors.forename: G J
authors.initials: GJ
authors.lastname: van der Bij
authors.forename: A K
authors.initials: AK
authors.lastname: Mels
authors.forename: R H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: S
authors.initials: S
authors.lastname: Meijer
authors.forename: M
authors.initials: M
authors.lastname: van Egmond
authors.forename: P A M
authors.initials: PA
authors.lastname: van Leeuwen
mesh_terms: D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000601:surgery; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D016898:Interferon-alpha / Q000627:therapeutic use*; D019990:Perioperative Care; D011183:Postoperative Complications / Q000276:immunology / Q000517:prevention & control
chemical_list: D007155:Immunologic Factors; D016898:Interferon-alpha