Fas ligand is expressed on human squamous cell carcinomas of the head and neck, and it promotes apoptosis of T lymphocytes

Recent reports have variously described expression of Fas ligand (FasL) or its absence in human tumors. The importance of the Fas-FasL mechanism for t he immune evasion by tumors provided a strong rationale for the examination of Fast expression and function in squamous cell carcinoma of the head and neck (SCCHN), which is one of the most immunosuppressive human cancers. Us ing immunostaining or immunoblotting, SCCHN cell lines and tumor biopsies w ere examined for the presence of the components of the Fas-FasL pathway and found to express Fas, as well as both the full-length and cleaved forms of Fast. By reverse transcription-PCR, mRNA for FasL and Fas were detected in all SCCHN tested, and cross-hybridization to radioactive Fas and Fast cDNA probes confirmed the specificity of amplification, To demonstrate that Fas t expressed on cell surface of SCCHN cells was biologically active, various SCCHN lines were coincubated with the Fas-sensitive Jurkat T-cell lines or activated peripheral blood mononuclear cells. Tumor-induced apoptosis of T cells was dependent on the ratio of tumor cells: lymphocytes. It was signi ficantly but only partially inhibited by neutralizing antibodies to Fast an d antagonistic antibodies to FasR. Tumor-induced apoptosis was enhanced by the pretreatment of tumor cells with metalloproteinase inhibitors, which in creased expression of Fast on tumor cells. Supernatants of tumor cells tran sduced with FasL also induced apoptosis of Jurkat cells. Thus, coincubation of SCCHN with Fas-sensitive lymphocytes can induce apoptosis of these lymp hocytes, and the Fas/FasL pathway appears to be responsible, at least in pa rt, for tumor-induced lymphocyte death, The data suggest that the Fas/FasL pathway is potentially immunosuppressive and may be involved in the escape of human carcinoma cells from immune destruction.