Enhancing effect of tumor necrosis factor (TNF)-α, but not IFN-γ, on the tumor-specific cytotoxicity of γδT cells from glioblastoma patients

Adoptive immunotherapy using tumor-specific killer cells can be beneficial in inducing regression of advanced cancer. The roles of cytokines on effector cells in inducing maximal killing activity and the accompanying side-effects should be investigated in vitro and fully understood prior to their clinical use. The present study indicates that the γδT cells involved in autologous tumor-specific killing consist of several populations in terms of their T cell receptor (TCR) repertoire, but predominantly express the products of the Vγ9/Vδ2 gene locus of the TCR. We then examined the effect of TNF-α and IFN-γ on these tumor-specific γδT cells for possible clinical use in cancer patients. TNF-α alone, at concentrations of 0.01–1.0 μg/ml, caused increased γδT cell cytotoxicity against autologous glioblastoma cells, whereas IFN-γ alone had no effect. The combination of TNF-α (1 μg/ml) with IL-2 (50 units/ml) resulted in further enhancement of cytotoxicity. TNF-α, but not IFN-γ, marginally inhibited the proliferative response of γδT cells; a similar result was seen when the cytokines were combined. TNF-α may, therefore, be one cytokine capable of inducing increased autologous tumor-specific activity in γδT cells, bearing mainly Vγ9/Vδ2 chains, which can be enhanced when combined with other cytokines.