Generation of potent T(h)1 responses from patients with lymphoid malignancies after differentiation of B lymphocytes into dendritic-like cells.
Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.
Mohty
Mohamad
M
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Université de la Méditerranée, 232 Boulevard Ste Marguerite, 13273 Marseille Cedex, France.
Isnardon
Daniel
D
Charbonnier
Aude
A
Lafage-Pochitaloff
Marina
M
Merlin
Michele
M
Sainty
Danielle
D
Olive
Daniel
D
Gaugler
Béatrice
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000494:pharmacology; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D002675:Child, Preschool; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000494:pharmacology; D019041:L-Selectin / Q000378:metabolism; D007938:Leukemia / Q000276:immunology* / Q000628:therapy; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D007952:Leukemia, Plasma Cell / Q000276:immunology; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism
D018941:Antigens, CD19; C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D019041:L-Selectin; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma