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A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients
Authors:Mikael G V Hanson  Volkan Özenci  Mattias C V Carlsten  Bengt L Glimelius  Jan-Erik A Frödin  Giuseppe Masucci  Karl-Johan Malmberg  Rolf V R Kiessling
Institution:(1) Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Institutet, R8:01, Karolinska Hospital, 171 76 Stockholm, Sweden;(2) Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden;(3) Department of Oncology (Radiumhemmet), Karolinska University Hospital Solna, Stockholm, Sweden;(4) Department of Oncology, Radiology and Clinical Immunology Akademiska sjukhuset Uppsala, Uppsala, Sweden
Abstract:Cancer patients with advanced disease display signs of immune suppression, which constitute a major obstacle for effective immunotherapy. Both T cells and NK cells are affected by a multitude of mechanisms of which the generation of reactive oxygen species is of major importance. Therefore, we hypothesized that two weeks of high-dose treatment with the anti-oxidant vitamin E may enhance NK cell function in cancer patients by protecting from oxidative stress. Seven patients with colorectal cancer (Dukes stage C and D) received a daily dose of 750 mg of vitamin E during a period of two weeks and the function, phenotype and receptor expression of NK cells were analyzed. The short-term vitamin E treatment significantly improved NK cell cytolytic activity in six out of the seven patients analyzed. The increased NK cell activity in patients’ PBMC was not due to increased numbers of NK cells or an increase in the proportion of the CD56dim NK cell subpopulation. Furthermore, neither an increased perforin expression nor an enhanced ability of NK cells to produce IFN-γ was observed as a result of vitamin E treatment. Finally, vitamin E treatment was associated with a minor, but consistent, induction of NKG2D expression in all patients analyzed. In conclusion, this pilot study demonstrates that vitamin E may boost NK cell function in patients with colorectal cancer. Further studies are warranted to explore the potential of vitamin E as an adjuvant for immunotherapy against cancer and to determine the underlying mechanism(s) behind vitamin E induced NK cell activation.
Keywords:Immune suppression  Colorectal cancer  Vitamin E  Natural killer cells  Tumor immunobiology
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