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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

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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.

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Acknowledgments

This work was supported by grants to R.K. from the Swedish Cancer Society, the Cancer Society of Stockholm, the European Union, the Karolinska Institutet, “ALF-project”-grant from the Stockholm City Council and National Institutes of Health (Grant CA102280). K-J.M. was supported by grants from the Cancer Society of Stockholm, the Swedish Society for Medical Research and the Swedish Children’s Cancer Foundation. G.M. was supported by grants from NORDFORSK-NCEV network (Grant 040226), the Cancer Society of Stockholm, and the King Gustaf V Jubilee Fund.

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Authors and Affiliations

  1. Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Institutet, R8:01, Karolinska Hospital, 171 76, Stockholm, Sweden

    Mikael G. V. Hanson, Volkan Özenci, Mattias C. V. Carlsten, Bengt L. Glimelius, Jan-Erik A. Frödin, Giuseppe Masucci & Rolf V. R. Kiessling

  2. Department of Medicine, Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

    Mattias C. V. Carlsten & Karl-Johan Malmberg

  3. Department of Oncology (Radiumhemmet), Karolinska University Hospital Solna, Stockholm, Sweden

    Jan-Erik A. Frödin

  4. Department of Oncology, Radiology and Clinical Immunology Akademiska sjukhuset Uppsala, Uppsala, Sweden

    Bengt L. Glimelius

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  1. Mikael G. V. Hanson
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  2. Volkan Özenci
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  3. Mattias C. V. Carlsten
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  8. Rolf V. R. Kiessling
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Correspondence to Rolf V. R. Kiessling.

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Hanson, M.G.V., Özenci, V., Carlsten, M.C.V. et al. A short-term dietary supplementation with high doses of vitamin E increases NK cell cytolytic activity in advanced colorectal cancer patients. Cancer Immunol Immunother 56, 973–984 (2007). https://doi.org/10.1007/s00262-006-0261-4

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  • DOI: https://doi.org/10.1007/s00262-006-0261-4

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