Determination of optimum vitamin D3 levels for NK cell-mediated rituximab- and obinutuzumab-dependent cellular cytotoxicity
Cancer Immunology, Immunotherapy, ISSN: 1432-0851, Vol: 67, Issue: 11, Page: 1709-1718
2018
- 9Citations
- 24Captures
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Metrics Details
- Citations9
- Citation Indexes9
- Captures24
- Readers24
- 24
Article Description
Vitamin D3 (25-OH-D3) deficiency impairs rituximab-dependent cellular cytotoxicity and the outcome of patients with diffuse large B-cell and follicular lymphomas (DLBCL). Since the optimum 25-OH-D3 serum levels for NK cell-mediated antibody-dependent cellular cytotoxicity (ADCC) are unknown, we determined the 25-OH-D3 serum levels associated with maximum NK cell-mediated ADCC. CD20 antibody-loaded CD20 B-cell lymphoma cell lines were cultured with NK cells and ADCC activity was determined by lactate dehydrogenase release assays. Using a newly developed formula, pre-defined 25-OH-D3 serum levels were achieved with high individual precision over a wide range. NK cells from 20 healthy individuals killed antibody-treated CD20 lymphoma cells in a concentration- and E:T ratio-dependent manner with obinutuzumab displaying a stronger ADCC activity than rituximab. Maximum NK-cell activity and ADCC were observed at 65 ng/ml 25-OH-D3, the middle of the normal range (30–100 ng/ml). 25-OH-D3 serum levels around this range should be the target in interventional trials aiming at improving NK cell-mediated ADCC by 25-OH-D3 substitution. Lower levels do not provide significant ADCC improvements in individuals with 25-OH-D3 deficiency or insufficiency and might result in the failure of interventions with 25-OH-D3.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85052134583&origin=inward; http://dx.doi.org/10.1007/s00262-018-2224-y; http://www.ncbi.nlm.nih.gov/pubmed/30132083; http://link.springer.com/10.1007/s00262-018-2224-y; https://dx.doi.org/10.1007/s00262-018-2224-y; https://link.springer.com/article/10.1007/s00262-018-2224-y
Springer Science and Business Media LLC
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