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Generation of Immature, Mature and Tolerogenic Dendritic Cells with Differing Metabolic Phenotypes
Published on: June 22, 2016
Generation of functional dendritic cells (DC) in adult acute lymphoblastic leukemia: rationale for a DC-based
Roberta Maggio1, Nadia Peragine, Elisabetta Calabrese
1Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy.
Insights
Dendritic cells (DC) from acute lymphoblastic leukemia (ALL) patients in remission can be effectively generated. These leukemia-specific DCs can stimulate immune responses, supporting potential DC-based vaccines for ALL patients.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Acute lymphoblastic leukemia (ALL) poses a significant challenge, even in remission.
- Dendritic cells (DCs) are crucial for initiating anti-tumor immune responses.
- The functionality of DCs derived from ALL patients requires investigation for therapeutic potential.
Purpose of the Study:
- To assess the capacity to generate effective dendritic cells (DCs) from adult ALL patients in complete remission (CR) and off-therapy.
- To evaluate the immune stimulatory potential of these patient-derived DCs loaded with leukemia-derived apoptotic bodies.
Main Methods:
- Monocyte-derived DCs were cultured using granulocyte-macrophage colony-stimulating factor, interleukin-4, and tumor necrosis factor-alpha.
- DC maturation markers, IL-12 production, and apoptotic body loading were assessed.
- Patient T and NK lymphocyte function was evaluated after stimulation.
- DCs loaded with leukemia-derived apoptotic bodies were tested for their ability to stimulate allogeneic and autologous lymphocytes.
Main Results:
- DCs generated from ALL patients in CR expressed maturation markers and produced IL-12 similarly to normal DCs.
- These DCs effectively loaded leukemia-derived apoptotic bodies.
- Patient T and NK lymphocytes exhibited normal function and cytokine production (TNF-alpha, interferon-gamma).
- Leukemia-loaded DCs enhanced stimulation of both allogeneic and autologous lymphocytes, generating specific anti-leukemic CD3+ cells.
Conclusions:
- Effective dendritic cells (DCs) can be generated from adult acute lymphoblastic leukemia (ALL) patients in complete remission.
- These DCs, when loaded with leukemia-derived apoptotic bodies, exhibit potent immune-stimulatory capabilities.
- These findings provide a strong rationale for developing DC-based vaccine strategies for ALL patients in CR to achieve disease control or eradication.
Abstract:
The capacity to generate effective dendritic cells (DC) from adult acute lymphoblastic leukemia (ALL) patients in complete remission (CR) and off-therapy was investigated. Monocyte-derived DC cultured in the presence of granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4 and tumor necrosis factor (TNF)-alpha expressed maturation markers, produced IL-12 and loaded apoptotic bodies to a similar extent to normal DC. Patients' circulating T and NK lymphocytes were normally represented and, after stimulation, were capable of producing TNF-alpha and interferon-gamma to a similar extent to control lymphocytes. DC loaded with leukemia-derived apoptotic bodies increased their ability to stimulate both allogeneic and autologous lymphocytes, and to generate specific anti-leukemic CD3 + cells. These findings offer a rationale for the design of DC-based vaccine programs for adult ALL patients in CR with the aim of controlling/eradicating the disease.

