Constitutive expression of functional 4-1BB (CD137) ligand on carcinoma cells

Members of the TNF superfamily, including Fas, Fas ligand, and CD40, have b een shown to be expressed on tumor cells. In the studies described in this work, we report that another family member, the ligand far 4-1BB (CD137), i s expressed on various human carcinoma cell lines, on cells of solid tumors derived from these cell lines, and cells obtained from human tumors. Expre ssion of 4-1BB ligand (4-1BBL) mRNA was detected by both RT-PCR and Norther n blot analysis, and expression of 4-1BBL protein was detected by Western b lot analysis of whole cell lysates and by FAGS analysis of tumor cells and cell lines. Incubation of tumor cells with a 4-1BB-Ig fusion protein led to the production of IL-8 by the cells, demonstrating that the 4-1BBL is func tionally active and signals back into the tumor cells. Furthermore, 4-1BBL expressed on the carcinoma cells functioned as a costimulatory molecule for the production of cytokines (most notably IFN-gamma) in cocultures of T ce lls and tumor cells. These findings suggest that 4-1BBL expressed on carcin oma cells may significantly influence the outcome of a T cell-tumor cell in teraction.