Potent antitumor activity of zoledronic acid-induced Vγ9Vδ2 T cells against primary effusion lymphoma

Primary effusion lymphoma (PEL) is a subtype of aggressive and resistant non-Hodgkin lymphoma that occurs predominantly in patients with advanced AIDS. In this study, we examined the antitumor activity of zoledronic acid (Zol)-induced Vγ9Vδ2 T cells against PEL cells in vitro and in vivo. Vγ9Vδ2 T cells recognized endogenous mevalonate metabolites and MICA/B of PEL cell lines, inducing cytotoxicity via granule exocytosis and TRAIL-mediated pathway. Vγ9Vδ2 T cells suppressed the development of PEL cells and existed in a PEL xenograft mouse model. These results show that immunotherapy with Zol-induced Vγ9Vδ2 T cells could demonstrate an efficient strategy for PEL.

► Vγ9Vδ2 T cells had the cytotoxic activity against PEL cells in vitro and in vivo.
► Mevalonate metabolites and MICA/B of PEL cells were recognized by Vγ9Vδ2 T cells.
► The cytotoxicity was mediated by granule exocytosis and TRAIL-mediated pathway.
► Vγ9Vδ2 T cells suppressed tumor growth and existed in a PEL xenograft mouse model.