# Modulation of Leukemic Blasts into Dendritic Cells (DCleu) and Their Role in Predicting Survival in Patients with AML and MDS

## TL;DR

This study shows that converting leukemic cells into dendritic cells can boost immune responses and predict survival in AML patients.

## Contribution

The study identifies DC/DCleu generation and immune activation as novel prognostic markers for AML.

## Key findings

- DC/DCleu effectively activate T cells and enhance anti-leukemic cytotoxicity.
- Higher DC/DCleu frequencies and specific cytokine patterns correlate with improved blast lysis and survival.
- Blast lysis levels are linked to overall survival in AML patients.

## Abstract

Ex vivo-generated dendritic cells (DC/DCleu) from leukemic whole blood or isolated PBMNCs effectively activate immune effector cells and enhance anti-leukemic cytotoxicity. Higher frequencies of DC/DCleu and distinct cytokine secretion patterns are associated with improved blast lysis and improved immune responses in vivo. These functional immune parameters correlate with overall survival of patients, underscoring the prognostic relevance of generated DC/DCleu. Thus, monitoring DC/DCleu generation and immune activation may provide valuable guidance for individualized immunotherapeutic strategies and improved treatment stratification in AML patients.

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. 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.