Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor beta 2.
Human glioblastoma cells secrete an inhibitory factor termed "glioblastoma-derived T-cell suppressor factor" (G-TsF). A member of the transforming growth factor beta (TGF beta) family, G-TsF is identical to TGF beta 2. The present study investigated the effect of G-TsF/TGF beta 2 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/TGF beta 2 and that the inhibitory effect could be reduced by using increasing concentrations of IL-2 (100 to 200 U/ml). Tumor necrosis factor alpha (TNF alpha) enhanced the IL-2-dependent proliferation of TIL's cultured in low concentrations of IL-2 (10 U/ml); however, neither TNF alpha nor interferon gamma was able to reduce the inhibitory effect of TGF beta 2 on TIL proliferation. In addition, TGF beta 2 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.
Kuppner
M C
MC
Department of Neurosurgery, Centre Hôpitalier Universitaire Vaudois, Lausanne, University Hospital, Zurich, Switzerland.
Hamou
M F
MF
Sawamura
Y
Y
Bodmer
S
S
de Tribolet
N
N
D001932:Brain Neoplasms / Q000276:immunology; D002455:Cell Division / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005909:Glioblastoma / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors / Q000494:pharmacology*
D007376:Interleukin-2; D010455:Peptides; D016212:Transforming Growth Factor beta; D015291:Transforming Growth Factors