Anti-Leukemic Effects Induced by Dendritic Cells of Leukemic Origin from Leukemic Blood Samples Are Comparable under Hypoxic vs. Normoxic Conditions

Author:

Doraneh-Gard Fatemeh12,Amberger Daniel Christoph3,Amend Carina12,Weinmann Melanie12,Schwepcke Christoph12,Klauer Lara12ORCID,Schutti Olga12,Hosseini Hedayatollah4ORCID,Krämer Doris5,Rank Andreas26ORCID,Schmid Christoph26,Schmetzer Helga Maria12

Affiliation:

1. Medical Department III, Working-group Immune-Modulation, Klinikum Großhadern, Ludwig-Maximilians-University, 81377 Munich, Germany

2. Bavarian Cancer Research Center (BZKF), 86156 Augsburg, Germany

3. First Department of Medicine, Paracelsus Medical University, 5020 Salzburg, Austria

4. Experimental Medicine and Therapy Research Department, Faculty of Medicine, University of Regensburg, 93040 Regensburg, Germany

5. Department of Hematology, Oncology and Palliative Care, Hospital Hagen, 58097 Hagen, Germany

6. Department of Hematology and Oncology, University Hospital of Augsburg, 86156 Augsburg, Germany

Abstract

Hypoxia can modulate the immune system by affecting the function and activity of immune cells, potentially leading to altered immune responses. This study investigated the generation of leukemia-derived dendritic cells (DCleu) from leukemic blasts and their impact on immune cell activation under hypoxic (5–10% O2) compared to normoxic (21% O2) conditions using various immunomodulatory Kits. The results revealed that DC/DCleu-generation was similar under hypoxic and normoxic conditions, with no significant differences observed in frequencies of generated DC/DCleu. Furthermore, the study showed that the activation of immune cells and their anti-leukemic activity improved when T cell-enriched immunoreactive cells were co-cultured with DC/DCleu which were generated with Kit I and M compared to the control after mixed lymphocyte cultures. The anti-leukemic activity was improved under hypoxic compared to normoxic conditions after MLCWB-DC Kit M. These findings suggest that DC/DCleu-cultures of leukemic whole blood with Kits under hypoxic conditions yield comparable frequencies of DC/DCleu and can even increase the anti-leukemic activity compared to normoxic conditions. Overall, this research highlights the potential of utilizing DC/DCleu (potentially induced in vivo with Kits) as a promising approach to enhance immune response in patients with acute myeloid leukemia.

Funder

DAAD

Publisher

MDPI AG

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