Potential of immunotherapies in the mediation of antileukemic responses for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) - With a focus on Dendritic cells of leukemic origin (DCleu)
CLINICAL IMMUNOLOGY
Authors: Ansprenger, Christian; Amberger, Daniel Christoph; Schmetzer, Helga Maria
Abstract
New (non-immunotherapeutic) treatment-strategies for AML/MDS-patients are under development. Dendritic cells (DCs) and 'leukemia-derived DC' (DCleu) connect the innate and the adaptive immunesystem and (re-)activate it, in their capacity as professional antigen-presenting cells (APCs). They can be generated ex vivo from peripheral blood mononuclear cells (PBMNCs) or whole blood (WB), containing the-physiological-cellular/soluble microenvironment of individual patients using various DC/DCleu-generating methods or (for WB) minimalized 'Kits', containing granulocyte-macrophage-colony-stimulating-factor (GM-CSF) and a second response-modifier. Proof for DC/DCleu-mediated activation of the immune-system after T-cell-enriched mixed lymphocyte culture (MLC) is done by flowcytometry, demonstrating increased fractions of certain activated, leukemia-specific or antileukemic cell-subsets of the innate and the adaptive immune-system. Generation of DC/DCleu is possible independent of patients' age, MHC-, mutation- or transplantation-status. In vivo-treatment of AML-/MDS-patients with blast-modulating, DC/DCleu- inducing 'Kits' could contribute to create migratory DCs, as well as antileukemically reactivated and memory-mediating immune-cells, which patrol tissue and blood and could contribute to stabilizing disease or remissions.
Development and function of human dendritic cells in humanized mice models
MOLECULAR IMMUNOLOGY
Authors: Anselmi, Giorgio; Helft, Julie; Guermonprez, Pierre
Abstract
Dendritic cells (DCs) are sentinel cells of the immune system arising from hematopoietic stem cells. DCs play a key role in the regulation of both adaptive and innate lymphocyte responses. As such, experimental models enabling a thorough analysis of human DCs development and function are needed. Humanized mice models (termed collectively as HIS mice, or human immune system mice models) provide unique opportunities to model human hematopoiesis and tackle the function of human immune cell types in vivo. Here, we review experimental approaches enabling to recapitulate the ontogeny of DC subsets in HIS mice and discuss studies addressing the biology of human DC subsets implementing HIS mice models.
COA
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