title: Functional monocyte-derived dendritic cells can be generated in chronic lymphocytic leukaemia.
abstract: Chronic lymphocytic leukaemia (CLL) remains an incurable disease. Although modern available treatments are able to induce disease regression, relapse almost inexorably occurs. Therefore, novel therapeutic strategies aimed at reducing the disease relapse rate are very much needed. Among these, the induction of tumour-associated antigen-specific cytotoxic T lymphocytes (CTL), through either DNA vaccines or injection of idiotype pulsed dendritic cells (DCs), has been actively investigated with encouraging preliminary results in B-cell malignancies. As the CLL B lymphocyte characteristically expresses low amounts of surface immunoglobulin (Ig) and T cells from these patients have been reported to display impaired functional activity, there are concerns related to the possibility of generating specific cytotoxic antitumoral T cells in this disease. In addition, no information is presently available regarding the functional ability of CLL-derived DCs. In the present work, freshly purified monocytes from CLL patients and normal donors were induced to differentiate in granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 serum-free medium and compared for their morphological, phenotypic and functional characteristics. Our results demonstrate that: (1) functional DCs can be generated from CLL patients with similar phenotype and function to those observed from normal donors; (2) in contrast to normal control subjects, monocyte-derived DCs from CLL patients spontaneously secrete endogenous IL-10; and (3) interferon (IFN)-gamma in combination with CD40L plays a major role in priming DCs from CLL patients for IL-12 and IL-15 production. Overall, these results indicate that it is possible to derive functionally competent DCs from circulating monocytes in CLL patients.
authors.affiliation: Unité d'Immuno-Hématologie et d'Immunopathologie, Institut Pasteur, 28 rue du Dr Roux, F-75724 Paris Cedex 15, France. vuillier@pasteur.fr
authors.forename: F
authors.initials: F
authors.lastname: Vuillier
authors.forename: K
authors.initials: K
authors.lastname: Maloum
authors.forename: E K
authors.initials: EK
authors.lastname: Thomas
authors.forename: C
authors.initials: C
authors.lastname: Jouanne
authors.forename: G
authors.initials: G
authors.lastname: Dighiero
authors.forename: D
authors.initials: D
authors.lastname: Scott-Algara
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000628:therapy; D009000:Monocytes / Q000166:cytology / Q000276:immunology
chemical_list: D016895:Culture Media, Serum-Free; D019409:Interleukin-15; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor