CD40 expressed on human melanoma cells mediates T cell co-stimulation and tumor cell growth |
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Authors: | Pirozzi G Lombari V Zanzi D Ionna F Lombardi M L Errico S Ruggiero G Manzo C |
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Affiliation: | Oncologia Sperimentale C-Immunologia, Istituto Nazionale dei Tumori Fondazione Pascale, Via M. Semmola, 80131 Napoli, Italy. |
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Abstract: | CD40 is a 50 kDa molecule, a member of the tumor necrosis factor/nerve growth factor receptor family. It is expressed on B cells, monocytes, dendritic cells and various malignant cells. While the critical relevance of this molecule in T cell-dependent B cell activation is already established, the biological role of CD40-CD154 interaction in non-hematopoietic cells is still unknown. Here we show that CD40 is functionally expressed on human melanoma-derived cell lines. No correlation between surface CD40 expression and the origin of the cell line, primary versus metastatic, was observed. Melanoma 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 structures, the involvement of additional pathways have to be postulated. We have identified 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 melanoma cell lines. |
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Keywords: | CD40 cell growth co-stimulation melanoma |
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