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International Immunology, Vol. 12, No. 6, 787-795, June 2000
© 2000 Japanese Society for Immunology

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

Giuseppe Pirozzi, Vincenza Lombari, Delia Zanzi2, Franco Ionna1, Maria Luisa Lombardi, Simona Errico, Giuseppina Ruggiero2 and Ciro Manzo

Oncologia Sperimentale C–Immunologia and
1 Oncologia Chirurgica B, Istituto Nazionale dei Tumori `Fondazione Pascale, Via M. Semmola, 80131 Napoli, Italy
2 Cattedra di Immunologia, Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università di Napoli `Federico II', via Pansini, 5-80131 Napoli, Italy

Correspondence to: G. Pirozzi

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.

Keywords: CD40, cell growth, co-stimulation, melanoma

Transmitting editor: G. Doria


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