Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor β2

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Abstract
✓ Human glioblastoma cells secrete an inhibitory factor termed “glioblastoma-derived T-cell suppressor factor” (G-TsF). A member of the transforming growth factor beta (TGFβ) family, G-TsF is identical to TGFβ2. The present study investigated the effect of G-TsF/TGFβ2 on the proliferative and cytotoxic properties of tumor-infiltrating lymphocytes (TIL's) isolated from malignant gliomas after expansion in vitro with interleukin-2 (IL-2). The results demonstrate that the IL-2 (5 to 20 U/ml)-dependent proliferative response of glioma-derived TIL's was inhibited 70% to 85% by G-TsF/TGFβ2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNFα) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNFα nor interferon gamma was able to reduce the inhibitory effect of TGFβ2 on TIL proliferation. In addition, TGFβ2 suppressed 60% to 100% the cytotoxic response of glioma-derived TIL's against several tumor targets, including autologous glioma cells, and the suppressive effect was shown to be reduced by increasing concentrations of IL-2.