B7.1 on human carcinomas: Costimulation of T cells and enhanced tumor-induced T-cell death

Human squamous cell carcinomas of the head and neck (SCCHN) do not express the costimulatory molecules B7.1 or B7.2 in situ or in culture. Transductio n of B7.1(-) SCCHN cells with the retroviral B7.1 and neo(r) genes resulted in the expression of high levels of the transgene in these tumor cells. Wh en B7.1(+) SCCHN cells were used as stimulators of autologous or allogeneic PBL in mixed lymphocyte-tumor cultures (MLTC), T-cell proliferation and ge neration of antitumor effector T cells as well as levels of their lytic act ivity were significantly increased. At the same time, a proportion of activ ated T cells seen to undergo apoptosis was found to be significantly higher upon coincubation with B7.1(+) SCC-HN than with B7.1(-) SCCHN. Both B7.1() and B7.1(-) SCCHN cells were found to express Fast on the cell surface an d in the cytoplasm, as well as mRNA for Fast and mRNA for TRAIL. However, e xpression of the B7.1 transgene did not lead to increased expression of Fas t protein on tumor cells. Yet, up to 50% of activated CD28(+) allogeneic T cells, which were CD95(+), showed evidence of DNA fragmentation in JAM and TUNEL assays upon incubation with an excess of B7.1(+) SCCHN for 24 h. Tumo r-induced T-cell death was equally and only in part blocked by anti-Fas ant ibodies in both B7.1(+) and B7.1 MLTC. While surface expression of B7.1 mol ecules on SCCHN cells enhanced T-cell costimulation via B7.1-CD28 interacti ons, it did not rescue activated T cells from tumor-induced apoptosis. The outcome of MLTC under these conditions was dependent on the ratio of tumor to T cells. Thus, in the presence of an excess of B7.1(+) tumor cells, acti vated T cells showed increased sensitivity to apoptosis which did not appea r to be Fas/ Fast mediated. These data are important for the development of B7.1 gene therapy and efforts directed at the generation of effector cells in MLTC. (C) 2000 Academic Press.