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Updated: Jun 10, 2026
Expansion of Human Peripheral Blood γδ T Cells using Zoledronate
Published on: September 9, 2011
Zoledronate stimulates gamma delta T cells in prostate cancer patients
Michio Naoe1, Yoshio Ogawa, Kumiko Takeshita
1Division of Urology, Showa University, Tokyo, Japan. naoe@east.cts.ne.jp
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.
Insights
Zoledronate (ZOL) activates gamma delta T cells, a type of immune cell, in prostate cancer patients. This immune stimulation may help reduce prostate-specific antigen (PSA) levels, offering a potential new avenue for cancer therapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Androgen deprivation therapy is standard for prostate cancer but often fails.
- New therapies are needed to slow prostate cancer progression.
- Bisphosphonates, like zoledronate (ZOL), treat bone metastases and may have anticancer effects by modulating immunity.
Purpose of the Study:
- To investigate the effect of zoledronate (ZOL) on gamma delta T cells.
- To assess ZOL's impact on serum prostate-specific antigen (PSA) levels and velocities.
- To explore ZOL's potential to enhance antitumor immune responses.
Main Methods:
- Examined the in vitro effect of ZOL, with and without IL-2, on gamma delta T cell activation.
- Analyzed the in vivo activation and number of gamma delta T cells in patients receiving ZOL for SRE prevention.
- Monitored changes in serum PSA levels and velocities before and after ZOL infusion.
Main Results:
- Zoledronate (ZOL) demonstrated in vitro activation of gamma delta T cells.
- IL-2 combined with ZOL further increased gamma delta T cell numbers in vitro.
- In vivo, ZOL activated peripheral blood gamma delta T cells.
- A reduction in serum PSA was observed in 3 of 11 patients post-ZOL treatment.
- A decrease in PSA velocity was noted in 5 of 10 patients after ZOL infusion.
Conclusions:
- Zoledronate (ZOL) stimulates gamma delta T cells both in vitro and in vivo.
- This immune stimulation by ZOL may contribute to an antitumor effect in prostate cancer.
- Findings suggest a role for gamma delta T cells in ZOL's potential anticancer activity.
