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Departments of
*
Immunology, Inflammation, and Pulmonary, and
Oncology Drug Discovery, Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, NJ 08543
Members of the TNF superfamily, including Fas, Fas ligand, and
CD40, have been shown to be expressed on tumor cells. In the studies
described in this work, we report that another family member, the
ligand for 4-1BB (CD137), is expressed on various human carcinoma cell
lines, on cells of solid tumors derived from these cell lines, and
cells obtained from human tumors. Expression of 4-1BB ligand (4-1BBL)
mRNA was detected by both RT-PCR and Northern blot analysis, and
expression of 4-1BBL protein was detected by Western blot analysis of
whole cell lysates and by FACS 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
functionally 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-
) in
cocultures of T cells and tumor cells. These findings suggest that
4-1BBL expressed on carcinoma cells may significantly influence the
outcome of a T cell-tumor cell interaction.
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