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Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells

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Abstract

Background

Hypovitaminosis D is associated with an adverse prognosis in colon cancer patients, possibly due to the effects of the vitamin on the immune system. Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to the anti-tumor effects of monoclonal antibodies, including cetuximab, an epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is frequently added to chemotherapy in the treatment of colon cancer.

Objective

The present study evaluates the association between vitamin D serum levels and the ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer cell lines.

Methods

Blood samples were obtained from 124 healthy volunteers and serum vitamin D was determined by RIA. NK cells were isolated from each sample and added to human colorectal carcinoma cells with or without cetuximab, and ADCC was assessed using a colorimetric lactate dehydrogenase assay.

Results

Correlation analysis indicates a significant, gender- and age-independent association between vitamin D levels and cetuximab-induced ADCC on HT29 cells, where NK cells from samples with vitamin D < 20 ng/mL are significantly less efficient in inducing ADCC. A confirmatory study on two additional colon cancer cell lines yielded similar results.

Conclusions

These data suggest that vitamin D supplementation in vitamin-deficient/insufficient colorectal cancer patients could improve cetuximab-induced ADCC.

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Acknowledgements

The Authors thank Ambra Fortunato, Marì De Leo and Emanuela Marras for technical support.

Author information

Author notes

  1. Lorenzo Mortara and Marzia B. Gariboldi contributed equally to this work

Authors and Affiliations

  1. Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, Università degli Studi dell’Insubria, Varese, Italy

    Lorenzo Mortara, Annalisa Bosi & Douglas M. Noonan

  2. Laboratory of Anticancer Pharmacology, Department of Biotechnology and Life Sciences, Università degli Studi dell’Insubria, Via L. Manara, 7 -, 21052, Busto Arsizio, VA, Italy

    Marzia B. Gariboldi & Elena Monti

  3. Medical Oncology, ASST Valle Olona, Busto Arsizio, Varese, Italy

    Marco Bregni

  4. Medical Oncology, ASST Sette Laghi, Varese, Italy

    Graziella Pinotti

  5. Department of Medicine and Surgery, Università degli Studi dell’Insubria, Varese, Italy

    Luigina Guasti, Alessandro Squizzato & Leonardo Campiotti

  6. Scientific and Technology Pole, IRCCS MultiMedica, Milan, Italy

    Douglas M. Noonan

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  1. Lorenzo Mortara
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Correspondence to Elena Monti.

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Funding

This study was supported by the Università degli Studi dell’Insubria, Fondi di Ateneo per la Ricerca “FAR 2014” and “FAR2015” (to LM) and the Italian Association for Cancer Research (AIRC- IG15895 to DN). The funding agencies were not involved in the research plan and the interpretation of the data.

Conflict of Interest

Lorenzo Mortara, Marzia Bruna Gariboldi, Annalisa Bosi, Marco Bregni, Graziella Pinotti, Luigina Guasti, Alessandro Squizzato, Douglas Noonan, Elena Monti, and Leonardo Campiotti declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

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Mortara, L., Gariboldi, M.B., Bosi, A. et al. Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular Cytotoxicity against Human Colon Carcinoma Cells. Targ Oncol 13, 657–665 (2018). https://doi.org/10.1007/s11523-018-0586-x

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  • DOI: https://doi.org/10.1007/s11523-018-0586-x

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