Glioblastoma cells potentiate the induction of the Th1-like profile in phosphoantigen-stimulated gamma delta T lymphocytes

ROSSO, DAVID A; ROSATO, MICAELA; ITURRIZAGA, JUAN; GONZALEZ, NAZARENO; SHIROMIZU, CAROLINA M; KEITELMAN, IRENE A; CORONEL, JUAN V; GOMEZ, FERNANDO; AMARAL, MARÍA MARTA; RABADAN, ALEJANDRA T; SALAMONE, GABRIELA V; JANCIC, CAROLINA C

Conferencia; The 9th International gamma delta T Cell Conference; 2021

γδ T lymphocytes are non-conventional T cells that participate in protective immunity and tumor surveillance. In healthy humans, the main subset of γδ T cells in peripheral blood express the TCR Vγ9Vδ2. This subset responds to non-peptide prenyl-pyrophosphate antigens such as (E)-4-hydroxy-3-methyl-but-enyl pyrophosphate (HMBPP). This unique feature of Vγ9Vδ2 T cells makes them a candidate for antitumor immunotherapy. In this study, we investigated the response of HMBPP-activated Vγ9Vδ2 T lymphocytes to glioblastoma multiforme (GBM) cells. For this purpose, human purified γδ T cells were stimulated with HMBPP (1 µM) and incubated with GBM cells (U251, U373, and primary GBM cultures) or their conditioned medium. After overnight incubation, the expressionof CD69 and perforin was evaluated by flow cytometry and cytokines production by ELISA. As well, we performed a meta-analysis of transcriptomic data obtained from The Cancer Genome Atlas (https://portal.gdc.cancer.gov). We observed, that HMBPPstimulated γδ T cells cultured with GBM or its conditioned medium, increased CD69, intracellular perforin, IFN-γ, and TNF-α production (p