Ex-Vivo Expanded Human Vγ9Vδ2 T Cells Efficiently Suppress Epithelial Ovarian Cancer Development

Abstract

Abstract The γδ-T cells attract attentions because of their potent cytotoxicity towards tumors. Most γδ-T cells facilitate the major histocompatibility complex (MHC)-independent activation by the interaction between their receptor Natural Killer Group 2 Member D (NKG2D) and MICA/MICB molecules expressed on the tumor cells, leading to tumor death. However, despite of the potent antitumor effects, their therapeutic efficiency and molecular mechanisms remain largely elusive. Ovarian cancer is one of the most lethal and challenging female malignancies worldwide because of the delayed diagnosis and the resistance to traditional chemotherapy, prompting us to investigate the immunotherapeutic effects of γδ-T cells as a new treatment. We successfully expanded γδ-T cells up to ~ 78% from peripheral blood mononuclear cells (PBMCs) with mostly Vγ9Vδ2-T cell subtype. We showed that the expanded γδ-T cells exerted significant cytotoxicity activities towards OVCAR3 and HTB75 cells in-vitro. Furthermore, in the tumor xenografts of NSG mice, γδ-T cells not only suppressed tumor growth but also completely eradicated the preexisting tumors with initial size ~5mm. Thus, we conclude that γδ-T cells possess dramatic cytotoxicity activities towards epithelial ovarian cancers both in-vitro and in-vivo, which strongly support the potential clinical immunotherapeutic application of γδ-T cells to treat this dreadful female malignancy.