Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients’ Response to Immunotherapy

Abstract

To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data:

Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients’ response to immunotherapy and graft-versus-host-disease could be defined.

Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients’ response to immunotherapy and graft-versus-host-disease.

Keywords:

• Dendritic cells
• acute myeloid leukaemia
• T-cells
• immunotherapy
• cytokines
• stem cell transplantation

Acknowledgements

The authors thank patients’ nurses and physicians on the wards for their support and Dr. Alexander Crispin (Department of Medical Informatics, Biometry, and Epidemiology, University of Munich) for statistical advices. Moreover, we thank the employees of the diagnostic laboratories for the patients’ diagnostic reports. The results presented in this manuscript were worked out in the doctoral theses of Christine Grabrucker, Anja Liepert, Marion Merle and Dorothea Fischbacher at the University Hospital Großhadern of the Ludwig-Maximilian-University Munich.

Disclosure statement

The authors report no declarations of interest.