Phenotypic and functional characterization of monocyte-derived dendritic cells in chronic lymphocytic leukaemia patients: influence of neoplastic CD19 cells in vivo and in vitro.
Dendritic cells (DCs) are the most potent antigen-presenting cells and are therefore an attractive option as antigen carriers in vaccination protocols. Chronic lymphocytic leukaemia (CLL) represents a potential good target for these approaches. The present study was designed to investigate the feasibility of generating in vitro fully functional DCs from peripheral blood (PB) monocytes of CLL patients at different phases of the disease. Although functional DCs could be obtained from CLL samples, in patients with active disease the expression of some co-stimulatory molecules appeared to be reduced. In contrast, DCs from CLL patients in remission showed no difference from those of normal controls. Moreover, patients with active disease produced DCs with reduced allostimulatory ability when compared with normal ones, whereas the functional capacities appeared to be restored in CLL DCs from remission patients. To more precisely assess the possible inhibitory effect of CLL cells on DC development, the influence of autologous leukaemic CD19(+) cells on the generation of monocyte-derived CLL DCs in vitro was investigated. The addition of CLL neoplastic cells markedly affected monocyte-derived DC maturation. In conclusion, monocytes from CLL patients with active disease give rise to DCs, which show phenotypic and functional defects that are not observed in remission CLL patients. These results need to be taken into account in the design of DC-based immunotherapeutic approaches in CLL.
Orsini
Enrica
E
Dipartimento di Biotecnologie Cellulari ed Ematologia, University La Sapienza, Rome, Italy. orsini@bce.uniroma1.it
Pasquale
Alessia
A
Maggio
Roberta
R
Calabrese
Elisabetta
E
Mauro
Francesca Romana
FR
Giammartini
Elena
E
Guarini
Anna
A
Foa
Robin
R
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000627:therapeutic use; D018941:Antigens, CD19 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000032:analysis; D019496:Cancer Vaccines; D016022:Case-Control Studies; D002999:Clone Cells; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D018941:Antigens, CD19; D000970:Antineoplastic Agents; D015415:Biomarkers; D019496:Cancer Vaccines; D000074323:Alemtuzumab; D000069283:Rituximab