title: Zoledronate stimulates gamma delta T cells in prostate cancer patients.
abstract: 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 first 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.
authors.affiliation: Division of Urology, Showa University, Tokyo, Japan. naoe@east.cts.ne.jp
authors.forename: Michio
authors.initials: M
authors.lastname: Naoe
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kumiko
authors.initials: K
authors.lastname: Takeshita
authors.forename: Jun
authors.initials: J
authors.lastname: Morita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shichijo
authors.forename: Khozo
authors.initials: K
authors.lastname: Fuji
authors.forename: Takashi
authors.initials: T
authors.lastname: Fukagai
authors.forename: Sanju
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Terao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007167:Immunotherapy; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077211:Zoledronic Acid; D017430:Prostate-Specific Antigen