Quality of T-cells after stimulation with leukemia-derived dendritic cells (DC) from patients with acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) is predictive for their leukemia cytotoxic potential

Liepert, Anja; Grabrucker, Christine; Kremser, Andreas; Dreyssig, Julia; Ansprenger, Christian; Freudenreich, M.; Kroell, Tanja; Reibke, Roland; Tischer, Johanna; Schweiger, C.; Schmid, Christoph; Kolb, Hans‐Jochem; Schmetzer, Helga

doi:10.1016/j.cellimm.2010.06.009

Cited by 29 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DCs were generated from blood samples according to a refined strategy culturing cells in a minimalized assay with 3 DC-generating methods (MCM-Mimic, Picibanil, Ca-Ionophore, Table 2) in parallel, as described by us. [31][32][33] All of the substances used for DC generation are approved for human treatment.…”

Section: Generationmentioning

confidence: 99%

“…However, there are still cases where no antileukemic function of T cells after DC stimulation could be achieved. 30,31 Thus, the aims of this study were as follows: (1) to evaluate compositions of several T reg subgroups (eg, CD4 + T reg , CD8 + T reg , T naive reg ) in uncultured peripheral bloodmononuclear cells from healthy probands and AML patients; (2) to investigate the development and recruitment of T reg subgroups during the stimulation of T cells with DC leu -containing DC ('DC') or blast-containing mononuclear cells ('MNC') in AML patients compared with healthy probands; (3) to correlate T-cell expression profiles with the antileukemic function of 'DC'-stimulated or 'MNC'-stimulated T cells in AML patients; and (4) to evaluate potential antileukemically predictive values of T reg subgroups.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Antileukemic T-cell Responses Can Be Predicted by the Composition of Specific Regulatory T-cell Subpopulations

Schick¹,

Vogt²,

Zerwes

et al. 2013

Journal of Immunotherapy

Self Cite

View full text Add to dashboard Cite

Summary: Regulatory T cells (T reg ) are important regulators of immune responses. In acute myeloid leukemia (AML) patients before/after immunotherapy (stem cell transplantation or donor lymphocyte infusion), their suppressive role can contribute to suppress severe graft-versus-host reactions, but also to impair antileukemic reactions. As leukemia-derived dendritic cells (DC leu ) are known to improve the antileukemic functionality of T cells, we evaluated the composition and development of distinct T reg subtypes in AML patients (n = 12) compared with healthy probands (n = 5) under unstimulated conditions and during stimulation with DC leu -containing DC (DC) or blast-containing mononuclear cells (MNC) in 0-to 7-day mixed lymphocyte cultures by flow cytometry. T-cell subgroups in AML patients were correlated with antileukemic functionality before and after DC or MNC stimulation by functional fluorolysis assays. (1) AML patients' T cells presented with significantly higher frequencies of T reg subgroups in unstimulated T cells compared with healthy probands. (2) After 7 days of DC or MNC stimulation, all T reg subtypes generally increased; significantly higher frequencies of T reg subtypes were still found in AML patients. (3) Antileukemic cytotoxicity was achieved in 36% of T cells after MNC compared with 64% after DC stimulation. Antileukemic activity after DC but not after MNC stimulation correlated with significantly lower frequencies of T reg subtypes (CD8 + T reg /T eff/em reg ). Furthermore, cut-off values for T reg subpopulations could be defined, allowing a prediction of antileukemic response. We demonstrate a crucial role of special T reg subtypes in the mediation of antileukemic functionality. High CD8 + T reg , T eff/em reg , and CD39 + T cells correlated clearly with a reduced antileukemic activity of T cells. DC stimulation of T cells contributes to overcome impaired antileukemic T-cell reactivity. Refined analyses in the context of clinical responses to immunotherapies and graft versus host reactions are required.

show abstract

Section: Generationmentioning

confidence: 99%

mentioning

confidence: 99%

Antileukemic T-cell Responses Can Be Predicted by the Composition of Specific Regulatory T-cell Subpopulations

Schick¹,

Vogt²,

Zerwes

et al. 2013

Journal of Immunotherapy

Self Cite

View full text Add to dashboard Cite

show abstract

“…Those T-cells (CD3 þ ), lateron used as effector cells, were positively isolated by MACS-technology, as described Liepert et al 2010). 1 Â 10 6 T-cells each were cultured in 1 ml RPMI-1640 medium (Biochrom, Berlin, Germany) containing 15% human serum (PAA, Pasching, Austria) and 50 U/ml IL-2 (Proleukin R5, Chiron), stimulated and restimulated twice (day 3 and 6 of culture) with either 2.5 Â 10 4 irradiated (20Gy) AML/MDS DC leu containing DC ('DC') or with the same amount of irradiated (20Gy) AML/MDS blast containing MNC ('MNC').…”

Section: Mixed Lymphocyte Culture (Mlc)mentioning

confidence: 99%

“…Proportions of positive events in defined gates compared with the isotype controls were calculated using Cell Quest software (Becton Dickinson, BD, Heidelberg, Germany). Quantification and characterization of DC and DC leu were performed by Flow cytometry according to our gating strategy already described by former groups (Schmetzer et al 2007;Kremser et al 2010;Liepert et al 2010;Grabrucker et al 2010;Dreyßig et al 2011). Flow cytometric analyses were carried out on day 0 and 10 followed by a functional cytotoxic fluorolysis assay on day 10 as described below.…”

Section: Mixed Lymphocyte Culture (Mlc)mentioning

confidence: 99%

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

Fischbacher¹,

Merle²,

Liepert³

et al. 2015

Cell Communication & Adhesion

Self Cite

View full text Add to dashboard Cite

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 ¼ 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-a, interferon-c) in supernatants of mixed-lymphocyte-culture and in serum (n ¼ 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. ARTICLE HISTORY

show abstract

“…In an attempt to further characterize the DC/DC leu-induced T cell response pattern, immunoscope spectratyping was used to detect T cell receptor (TCR) rearrangements in combination with functional flow cytometry and a non-radioactive fluorolysis assay. Results indicated that a combined strategy using spectratyping with functional tests might not only provide useful information about the specificity and efficacy of the induced T cell response but also pave the way to effective T cell clones for therapy (85).…”

Section: Quantity and Quality Control Of Leukemia-derived Dcsmentioning

confidence: 99%

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

Yuan

Song

Jiang

2012

Intractable Rare Dis Res

View full text Add to dashboard Cite

Quality of T-cells after stimulation with leukemia-derived dendritic cells (DC) from patients with acute myeloid leukemia (AML) or myeloid dysplastic syndrome (MDS) is predictive for their leukemia cytotoxic potential

Cited by 29 publications

References 28 publications

Antileukemic T-cell Responses Can Be Predicted by the Composition of Specific Regulatory T-cell Subpopulations

Antileukemic T-cell Responses Can Be Predicted by the Composition of Specific Regulatory T-cell Subpopulations

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

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

Contact Info

Product

Resources

About