Zoledronate Stimulates gamma delta T Cells in Prostate Cancer Patients

Androgen deprivation therapy is the mainstay of treatment for prostate cancer Given its frequent failure, new therapy that reduces prostate cancer progression would be a breakthrough in treating this disease Bisphosphonates are well-established agents for treating skeletal-related events (SREs) in prostate cancer patients with bone metastases Exposure to bisphosphonates may not only reduce the incidence of SREs, but also have anticancer effects by modulating a patient's immunity The purpose of this study was to examine the effect of zoledronate (ZOL) on gamma delta T cells. serum prostate-specific antigen (PSA) levels, and velocities The effect of ZOL, with and without IL-2, on gamma delta T cell activation was examined in vitro. Furthermore, the activated state and the number of gamma delta T cells and changes in serum PSA levels were examined for patients who received ZOL infusion for the prevention of SREs We found that ZOL activated gamma delta T cells, and the number of gamma delta T cell was increased when IL-2 was administered with ZOL in vitro Comparisons before and after the lust ZOL infusion revealed that gamma delta T cells in peripheral blood were activated by ZOL Moreover, after the first ZOL treatment, reduction in serum PSA was observed in 3 of 11 patients, and reduction in PSA velocity was observed in 5 of 10 patients Our findings indicate that ZOL stimulates gamma delta T cells in vivo and in vitro This study provides further insight into the ability of gamma delta T cells to induce an antitumor immune response