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Human γδT cell immunotherapy is well tolerated and has shown promising results in clinical trials; however, its antitumor efficacy is limited, including results in solid tumors. expanded γδT cell stimulated by zoledronic acid (ZOL) activates the γδT cell subpopulation of so called Vγ9Vδ2 T cells. To improve the clinical outcomes of Vγ9Vδ2 T cell (abbreviated as γδT cell here) immunotherapy, we aimed to increase the cytotoxicity of γδT cells by focusing on two issues: recognition of tumor cells by γδT cells and the effector (γδT cell)-to-target (tumor cell) (E/T) ratio.expanded γδT cells showed potent cytotoxicity against urinary bladder cancer (UBC) cells in assays. Combination treatment with standard anticancer agents showed that low dose gemcitabine pretreatment significantly enhanced the cytotoxicity of γδT cells by upregulating the expression of and (), which are tumor-associated antigens recognized by γδT cells. These effects were abrogated by small interfering RNA-mediated knockdown of in UBC cells, suggesting that pre-exposing cancer cells to anticancer agents could be a promising strategy. A bladder instillation approach was used to increase the E/T ratio. The efficacy of-expanded γδT cell immunotherapy was examined in an orthotopic xenograft model. In Vivo Imaging System analysis revealed the potent cytotoxicity of weekly intravesical administration of γδT cells, and weekly gemcitabine pretreatment enhanced the cytotoxicity of γδT cells . In conclusion, intravesical γδT cell immunotherapy and combination therapy with low dose gemcitabine may be a promising strategy in UBC.

Background/Aim: γδ T cells mediate cytotoxicity against prostate cancer (PCa) cells in vitro; however, the clinical efficacy of γδ T cell-targeted immunotherapy for recurrent and metastatic PCa is unsatisfactory. We hypothesized that the resistance of recurrent and metastatic PCa to γδ T cells is related to the presence of prostate cancer stem cells (PCSCs), and we examined their relationship. Materials and Methods: PCa spheres (prostaspheres) were generated from five PCa cell lines, and their susceptibility to cytotoxicity by γδ T cells was investigated. Expression of stemness-related markers was evaluated by qRT-PCR. Results: Prostasphere-derived cancer cells were resistant to lysis by γδ T cells and expressed higher levels of several stemness markers, including CD133, NANOG, SOX2, and OCT4, than the parental PCa cell lines. Conclusion: Ex vivo-expanded γδ T cells are not effective against PCSCs.

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