IMMU-15. HUMAN ALLOGENIC γδ T CELLS KILL PATIENT-DERIVED GLIOBLASTOMA CELLS IN A PVR- AND DNAM-1-DEPENDENT MANNER

Abstract

Abstract Background Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand–receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand–receptor interactions and provide a basis for using γδ T cells to treat glioblastoma. METHODS Vγ9Vδ2 T cells were generated from peripheral blood mononuclear cells of healthy donors using artificial antigen presenting cells. MICA, ULBP, PVR and Nectin expression in 10 patient-derived glioblastoma (PDG) cell lines were analyzed. The in vitro cytokine secretion from the γδ T cells and their cytotoxicity toward the PDG cell lines were also analyzed. The in vivo anti-tumor effects were evaluated using a U87 orthotopic xenograft glioblastoma model. RESULTS Expression of ligands and cytotoxicity of the γδ T cells varied among the PDG cell lines. Interestingly, cytotoxicity correlated significantly with the PVR expression of the PDG cells. IFN-γ and granzyme B secretion levels were significantly higher when γδ T cells were co-cultured with high PVR–expressing PDG cells than when they were co-cultured with low PVR–expressing PDG cells. Blocking DNAM-1 resulted in a decrease in γδ T cell–mediated cytotoxicity and cytokine secretion. Intratumoral injection of γδ T cells showed anti-tumor effects in an orthotopic mouse model. Conclusions Allogenic γδ T cells showed potent anti-tumor effects on glioblastoma in a PVR- and DNAM-1-dependent manner. Our findings will facilitate the development of clinical strategies using γδ T cells for glioblastoma treatment.