Tumor-induced apoptosis of T lymphocytes: elucidation of intracellular apoptotic events

Our recent studies suggest that human squamous cell carcinoma of the head a nd neck (SCCHN) is capable of activating an intrinsic mechanism of programm ed-cell death in interacting lymphocytes in situ and in vitro. The current study used Jurkat T-cell line as a model to investigate intracellular apopt otic events in T cells interacting with SCCHN. Apoptosis induced in T lymph ocytes by tumor cells was in part Fas-mediated, since it was partially, but significantly inhibited in the presence of anti-fas ligand Ab or in Fas-re sistant Jurkat cells. The synthetic caspase inhibitors, N-benzyloxycarbonyl -Val-Ala-Asp-fluoromethyl ketone (Z-VAD-FMK) and N-benzyloxycarbonyl-Asp-gl u-caspase-3 substrate, and in cleavage of TcR-zeta chain, shown by us to be a T-cell specific caspase-3 substrate. Overexpression of Bcl-2 did not pro vide protection of T cells from SCCHN-induced DNA degradation. Instead, the Bcl-2 protein was cleaved in the target T cells during their co-incubation with tumor cells. These findings demonstrate that tumor cells can trigger in T lymphocytes caspase-dependent apoptotic cascades, which are not effect ively protected by Bcl-2, (C) 2000 by The American Society of Hematology.