biostudies-literatureWang HNCI NIH HHSNIHNIGMS NIH HHSe003339https://www.ebi.ac.uk/biostudies/studies/S-EPMC8705233biostudies-literatureUnknown9(12)<h4>Background</h4>Gamma delta (γδ) T cells are attractive effector cells for cancer immunotherapy. Vδ2 T cells expanded by zoledronic acid (ZOL) are the most commonly used γδ T cells for adoptive cell therapy. However, adoptive transfer of the expanded Vδ2 T cells has limited clinical efficacy.<h4>Methods</h4>We developed a costimulation method for expansion of Vδ2 T cells in PBMCs by activating γδ T-cell receptor (γδTCR) and Toll-like receptor (TLR) 7/8 using isopentenyl pyrophosphate (IPP) and resiquimod, respectively, and tested the functional markers and antitumoral effects in vitro two-dimensional two-dimensional and three-dimensional spheroid models and in vivo models. Single-cell sequencing dataset analysis and reverse-phase protein array were employed for mechanistic studies.<h4>RJournal for immunotherapy of cancerCostimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function.PMC8705233CA114046P50 CA261608Tara Miller Melanoma FoundationP30 CA016672P30 CA010815P01 CA114046R35 GM141832P50 CA174523CA170340Zhang GMitchell TCFan YHerlyn MZhang JSomasundaram RConnelly TGuo WDong LWang HChen HLiu SHuang LLi LScholler JChoi RJune CHLu HOu LYeye GTian SHuang AXu XMills GBfalseCostimulation of γδTCR and TLR7/8 promotes Vδ2 T-cell antitumor activity by modulating mTOR pathway and APC function.<h4>Background</h4>Gamma delta (γδ) T cells are attractive effector cells for cancer immunotherapy. Vδ2 T cells expanded by zoledronic acid (ZOL) are the most commonly used γδ T cells for adoptive cell therapy. However, adoptive transfer of the expanded Vδ2 T cells has limited clinical efficacy.<h4>Methods</h4>We developed a costimulation method for expansion of Vδ2 T cells in PBMCs by activating γδ T-cell receptor (γδTCR) and Toll-like receptor (TLR) 7/8 using isopentenyl pyrophosphate (IPP) and resiquimod, respectively, and tested the functional markers and antitumoral effects in vitro two-dimensional two-dimensional and three-dimensional spheroid models and in vivo models. Single-cell sequencing dataset analysis and reverse-phase protein array were employed for mechanistic studies.<h4>R2021-01-01T00:00:00Z2021 Dec2026-06-17T06:26:07.206Z2022-02-11T15:11:43.237ZS-EPMC87052333493774210.1136/jitc-2021-003339