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

• Published in: Cancer letters 1999-06, Vol.140 (1-2), p.161-167
• Main Authors: Suzuki, Youichi, Fujimiya, Yoshiaki, Ohno, Tadao, Katakura, Ryuichi, Yoshimoto, Takashi
• Format: Article
• Language: English
• ISSN: 0304-3835
• DOI: 10.1016/S0304-3835(99)00067-1

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 gamma delta T 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 V gamma 9/V delta 2 gene locus of the TCR. We then examined the effect of TNF- alpha and IFN- gamma on these tumor-specific gamma delta T cells for possible clinical use in cancer patients. TNF- alpha alone, at concentrations of 0.01-1.0 mu g/ml, caused increased gamma delta T cell cytotoxicity 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 cells; a similar result was seen when the cytokines were combined. TNF- alpha may, therefore, be one cytokine capable of inducing increased autologous tumor-specific activity in gamma delta T cells, bearing mainly V gamma 9/V delta 2 chains, which can be enhanced when combined with other cytokines.