Zoledronic acid sensitizes rhabdomyosarcoma cells to cytolysis mediated by human gamma delta T cells

摘要

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 gamma delta T cells on RMS cell lines was evaluated and the molecular interactions involved were investigated. gamma delta 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 gamma delta T cells against RMS was assessed in vitro and in vivo. gamma delta T cells were cytotoxic to RMS cells. Importantly, Zol markedly increased their cytotoxic potential. RMS cells treated with Zol-stimulated gamma delta T cells to produce interferon gamma. gamma delta T cell-mediated cytotoxicity was primarily through the T cell receptor-dependent signaling pathway in blocking studies. Transfer of gamma delta 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 gamma delta T cells in RMS.