Reduced expression of the mevalonate pathway enzyme farnesyl pyrophosphate synthase unveils recognition of tumor cells by vγ9vδ2 T cells

Abstract

Human Vγ9Vδ2 T cells are characterized by a unique specificity for certain tumors (e.g., Daudi), cells presenting so-called phosphoantigens such as isopentenyl pyrophosphate (IPP), or cells treated with aminobisphosphonates. We now report conversion of hematopoietic and nonhematopoietic tumor cell lines into Vγ9Vδ2 T cell activators by means of short hairpin RNA-mediated knockdown of expression of the IPP-consuming enzyme, farnesyl pyrophosphate synthase (FPPS). FPPS knockdown cells activated Vγ9Vδ2 T cells, as measured by increased levels of CD69 and CD107a, killing of FPPS knockdown cells, and induction of IFN-γ secretion. The IPP-synthesis-inhibiting drug mevastatin reduced Vγ9Vδ2 T cell ..