Zoledronic acid sensitizes rhabdomyosarcoma cells to cytolysis mediated by human γδ T cells

Sun,Ling‑Ling; Zhang,Zheng‑Liang; Li,Ying‑Jun; Wang,Sheng‑Dong; Li,Heng‑Yuan; Li,Bing‑Hao; Zhu,Ting; Ye,Zhao‑Ming

doi:10.3892/ol.2017.6894

Zoledronic acid sensitizes rhabdomyosarcoma cells to cytolysis mediated by human γδ T cells

Authors:
- Ling‑Ling Sun
- Zheng‑Liang Zhang
- Ying‑Jun Li
- Sheng‑Dong Wang
- Heng‑Yuan Li
- Bing‑Hao Li
- Ting Zhu
- Zhao‑Ming Ye
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Affiliations: Department of Orthopedics, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Department of Epidemiology and Health Statistics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Published online on: September 6, 2017 https://doi.org/10.3892/ol.2017.6894
Pages: 5597-5604

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Abstract

Rhabdomyosarcoma (RMS) is the most common type of soft‑tissue sarcoma in children. Immunotherapy has been proposed as a treatment for this deadly tumor. In the present study, the cytotoxicity of ex vivo expanded γδ T cells on RMS cell lines was evaluated and the molecular interactions involved were investigated. γδ T cells were expanded in vitro using peripheral blood mononuclear cells from 5 healthy donors and were stimulated with zoledronic acid (Zol) and interleukin 2. RMS cell lines RD and A‑673 were used as target cells. The cytotoxicity of the γδ T cells against RMS was assessed in vitro and in vivo. γδ T cells were cytotoxic to RMS cells. Importantly, Zol markedly increased their cytotoxic potential. RMS cells treated with Zol‑stimulated γδ T cells to produce interferon γ. γδ T cell‑mediated cytotoxicity was primarily through the T cell receptor‑dependent signaling pathway in blocking studies. Transfer of γδ T cells together with Zol into nude mice induced the regression of RD tumor xenotransplants. The results of the present study provide the rationale for the clinical evaluation of γδ T cells in RMS.

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