Enhancing effect of tumor necrosis factor (TNF)-alpha, but not IFN-gamma, on the tumor-specific cytotoxicity of gamma delta T cells from glioblastomapatients

Adoptive immunotherapy using tumor-specific killer cells can be beneficial in inducing regression of advanced cancer. The roles of cytokines on effect or cells in inducing maximal killing activity and the accompanying side-eff ects should be investigated in vitro and fully understood prior to their cl inical use. The present study indicates that the gamma delta T cells involv ed in autologous tumor-specific killing consist of several populations in t erms of their T cell receptor (TCR) repertoire, but predominantly express t he products of the V gamma 9/V delta 2 gene locus of the TCR. We then exami ned the effect of TNF-alpha and IFN-gamma on these tumor-specific gamma del ta T cells for possible clinical use in cancer patients. TNF-alpha alone, a t concentrations of 0.01-1.0 mu g/ml, caused increased gamma delta T cell c ytotoxicity against autologous glioblastoma cells, whereas IFN-gamma alone had no effect. The combination of TNF-alpha (1 mu g/ml) with IL-2 (50 units /ml) resulted in further enhancement of cytotoxicity. TNF-alpha but not IFN -gamma, marginally inhibited the proliferative response of gamma delta T ce lls; a similar result was seen when the cytokines were combined. TNF-alpha may, therefore, be one cytokine capable of inducing increased autologous tu mor-specific activity in gamma delta T cells, bearing mainly V gamma 9/N de lta 2 chains, which can be enhanced when combined with other cytokines. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.