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 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.
Pirozzi
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G
Oncologia Sperimentale C-Immunologia, Istituto Nazionale dei Tumori Fondazione Pascale, Via M. Semmola, 80131 Napoli, Italy.
Lombari
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V
Zanzi
D
D
Ionna
F
F
Lombardi
M L
ML
Errico
S
S
Ruggiero
G
G
Manzo
C
C
D019013:CD40 Antigens / Q000032:analysis* / Q000502:physiology; D023201:CD40 Ligand; D002455:Cell Division; D006801:Humans; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand