Abstract
Dendritic cells (DC) can facilitate immune responses that might help in the induction of effective antitumor T cell responses. We reported previously that leukemic blasts from selected patients with acute myeloid leukemia (AML) were able to differentiate in vitro into cells with mature DC features. However, despite the use of a wide variety of cytokine combinations, leukemic DC could not be obtained from all AML patients. In this study, we investigated in a wide range of AML patients (n = 30), the nature and functional characteristics of the blast compartment that can be induced to acquire DC features in vitro. Our results demonstrate that leukemic DC generated in the presence of GM-CSF, IL-4 and matured with CD40L, are composed of two major subsets: DC derived from CD14+ leukemic cells and leukemic DC derived from in vivo expanded circulating blood myeloid DC (MDC). Leukemic DC of both subsets exhibited DC morphology, had a phenotype of mature DC, and could induce a potent proliferative response of naive CD4+ T cells. Moreover, both subsets produced large amounts of IL-12p70 and leukemic CD14+-derived DC could induce a potent Th1 response. These results can be considered as a prerequisite before the design of vaccine immunotherapy protocols for the adjuvant treatment of AML patients.
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Acknowledgements
MM was supported by a grant from the ‘Fondation de France’, Paris, France and from the SFGM-TC, Lyon, France. We thank C Mawas (INSERM U119) and D Maraninchi (Institut Paoli-Calmettes) for helpful discussions. We thank D Jarrossay, J Benfares and J Wolfers (Immunotech, Beckman-Coulter, Marseille) for kindly providing the ILT3 mAb. We also thank R Galindeau for assistance in cell sorting; S Just-Landi and N Baratier for excellent technical assistance.
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Mohty, M., Isnardon, D., Blaise, D. et al. Identification of precursors of leukemic dendritic cells differentiated from patients with acute myeloid leukemia. Leukemia 16, 2267–2274 (2002). https://doi.org/10.1038/sj.leu.2402706
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DOI: https://doi.org/10.1038/sj.leu.2402706
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