CD40 expressed on human melanoma cells mediates T cell co-stimulation and tumor cell growth

CD40 is a 50 kDa molecule, a member of the tumor necrosis factor/nerve grow th factor receptor family, It is expressed on B cells, monocytes, dendritic cells and various malignant cells. While the critical relevance of this mo lecule in T cell-dependent B cell activation is already established, the bi ological role of CD40-CD154 interaction in non-hematopoietic cells is still unknown, Here we show that CD40 is functionally expressed on human melanom a-derived cell lines. No correlation between surface CD40 expression and th e origin of the cell line, primary versus metastatic, was observed, Melanom a cells were shown to be able to co-stimulate TCR-triggered human T cells; moreover, because they do not express CD80 or CD86 co-stimulatory structure s, the involvement of additional pathways have to be postulated, We have id entified CD40 as one of the molecules involved in melanoma cell-mediated co -stimulation of anti-CD3-triggered human CD4(+) T lymphocytes, In addition, a CD40-dependent pathway, able to enhance tumor cell proliferation at low serum concentrations, in vitro, has been shown to be functional in human me lanoma cell lines.