Lorenzo Mortara1, Marzia B Gariboldi2, Annalisa Bosi1, Marco Bregni3, Graziella Pinotti4, Luigina Guasti5, Alessandro Squizzato5, Douglas M Noonan1,6, Elena Monti7, Leonardo Campiotti5. 1. Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, Università degli Studi dell'Insubria, Varese, Italy. 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. 3. Medical Oncology, ASST Valle Olona, Busto Arsizio, Varese, Italy. 4. Medical Oncology, ASST Sette Laghi, Varese, Italy. 5. Department of Medicine and Surgery, Università degli Studi dell'Insubria, Varese, Italy. 6. Scientific and Technology Pole, IRCCS MultiMedica, Milan, Italy. 7. Laboratory of Anticancer Pharmacology, Department of Biotechnology and Life Sciences, Università degli Studi dell'Insubria, Via L. Manara, 7 -, 21052, Busto Arsizio, VA, Italy. elena.monti@uninsubria.it.
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.
BACKGROUND: Hypovitaminosis D is associated with an adverse prognosis in colon cancerpatients, 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 humancolorectal 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 cancerpatients could improve cetuximab-induced ADCC.
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