Exposure to myeloma cell lysates affects the immune competence of dendritic cells and favors the induction of Tr1-like regulatory T cells.
The aim of this work was to investigate the interactions of tumor cells with dendritic cells (DC) in normal donors and patients with multiple myeloma (MM). Normal and MM DC internalized necrotic lysates derived from myeloma cell lines (MCL) with high efficiency, whereas necrotic lysates from primary myeloma cells (PMC) were internalized with significantly lower efficiency. A positive correlation was found between susceptibility to internalization and the ability to induce DC maturation. After PMC exposure, DC produced large amounts of IL-10 and measurable amounts of IL-4 but no detectable IL-12. Two rounds of exposure to PMC-treated DC generated autologous T cells with low proliferative capacity, decreased IFN-gamma production and increased IL-10 production in the absence of IL-4 production. These data indicate that myeloma cells can affect host immunity by priming DC towards a maturation state favoring the generation of T cells with a regulatory rather than an effector phenotype.
Fiore
Francesca
F
Divisione di Ematologia dell'Università di Torino, Torino, Italy.
Nuschak
Barbara
B
Peola
Silvia
S
Mariani
Sara
S
Muraro
Michela
M
Foglietta
Myriam
M
Coscia
Marta
M
Bruno
Benedetto
B
Boccadoro
Mario
M
Massaia
Massimo
M
D002454:Cell Differentiation / Q000276:immunology; D002457:Cell Extracts / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D009101:Multiple Myeloma / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D002457:Cell Extracts