Daniel Christoph Amberger, Zuzana Fischer, Diana Deen, Anika Hirn-Lopez, Caroline Plett, Alexander Rabe, Christoph Schwepcke, Selda Ugur, Lara Kristina Klauer, Christian Ansprenger, Anja Liepert, Markus Freudenreich, Christoph Schmid, Helga Maria Schmetzer
- Background/objectives: Acute myeloid leukemia (AML) is characterized by impaired anti-leukemic immune responses, and the ex vivo or in vivo generation of dendritic cells (DCs), including leukemic dendritic cells (DCleu), represents a promising strategy to stimulate immune cells and improve anti-leukemic activity.
Methods: This study examined the generation, phenotype and functional relevance of DCs and DCleu produced ex vivo from blast-containing PBMNCs and whole blood (WB) in AML. Using both standard DC/DCleu-generating protocols and available Kits.
Results: We show that DC/DCleu can be reliably generated with both methods. Generated DC/DCleu effectively activated T cells during mixed lymphocyte cultures (MLCs), resulting in enhanced anti-leukemic cytotoxicity. Improved blast lysis correlated with specific immunological features, including higher frequencies of generated DCleu and mature DC subsets, as well as a certain cytokine pattern after DC/DCleu cultures or MLC. InBackground/objectives: Acute myeloid leukemia (AML) is characterized by impaired anti-leukemic immune responses, and the ex vivo or in vivo generation of dendritic cells (DCs), including leukemic dendritic cells (DCleu), represents a promising strategy to stimulate immune cells and improve anti-leukemic activity.
Methods: This study examined the generation, phenotype and functional relevance of DCs and DCleu produced ex vivo from blast-containing PBMNCs and whole blood (WB) in AML. Using both standard DC/DCleu-generating protocols and available Kits.
Results: We show that DC/DCleu can be reliably generated with both methods. Generated DC/DCleu effectively activated T cells during mixed lymphocyte cultures (MLCs), resulting in enhanced anti-leukemic cytotoxicity. Improved blast lysis correlated with specific immunological features, including higher frequencies of generated DCleu and mature DC subsets, as well as a certain cytokine pattern after DC/DCleu cultures or MLC. In addition, the frequencies of proliferating T cells after MLC strongly correlated with the degree of achieved blast lysis, underscoring the importance of efficient DC/DCleu-mediated T cell stimulation. Both the frequencies of generated DC/DCleu and the resulting blast lytic activity were linked to overall survival (OS) in AML patients. Individuals who failed to demonstrate improved blast lysis exhibited significantly reduced OS, suggesting inadequate immune responsiveness of patients in vivo.
Conclusions: These findings identify phenotypic and functional immune parameters as predictors of clinical outcome and highlight the prognostic relevance of ex vivo immune profiling. This approach may help to optimize and personalize future immunotherapeutic strategies in AML.…
