The effects of zoledronate on monocyte-derived dendritic cells from melanoma patients differ depending on the clinical stage of the disease

Abstract

Zoledronic acid has shown indirect anticancer effects on angiogenesis, the tumor microenvironment and immune responses. Its immunological action is exerted, at least in part, via its modulating properties. The aim of this study was to investigate the in vitro effects of zoledronic acid on the dendritic cells of melanoma patients. Peripheral blood samples were collected from 26 patients with melanoma and 11 healthy donors. Dendritic cells were derived from purified monocytes, and zoledronic acid (ZA) was added on the first day of culture. The phenotype and function of the generated cells were evaluated by flow cytometry. The ZA-treated monocytes from patients with early-stage disease generated DCs characterized by reduced endocytic activity and increased allostimulatory capacity compared with the untreated samples, allowing restoration of the DC function observed in normal subjects. In contrast, the ZA-treated monocytes from patients at stage III generated cells with higher CD14 antigen expression and endocytosis than the untreated samples. Therefore, in melanoma patients, the in vitro ZA effects differ according to the progression of the disease. In addition, our preliminary results appear to suggest that ZA effects are also influenced by the expression of CD14 antigen, indicating that the DC phenotype together with clinical characteristics must be considered in the choice of patients to be treated with ZA. Our work focus on the effect of ZA on monocyte-derived DCs from melanoma patients, showing that the effects of therapeutic doses of this drug might be mediated at least in part by modulation of myeloid cell function.

Keywords:

• melanoma
• dendritic cells
• zoledronic acid

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We express our sincere appreciation to the study participants.

Funding

This work was supported by Novartis Farma (Origgio, Italy) and University of Pisa. A.F. was supported by a fellowship of the Associazione Contro il Melanoma Onlus (Pisa, Italy).

Author Contributions

All listed authors have reviewed and approved the final version of the manuscript. All authors contributed to the work presented in this paper. Conceived and designed the experiments: A.L., A.R., R.C. Performed the experiments: A.F., G.O. Analyzed the data: A.F., A.L. Recruited the patients: A.R. Wrote the paper: A.F., A.L., R.C. Discussed the results and implications: A.F., A.L., A.R., R.C.