Leukemia derived dendritic cell (DCleu) mediated immune response goes along with reduced (leukemia-specific) regulatory T-cells
Pepeldjiyska E, Li L, Gao J, Seidel CL, Blasi C, Özkaya E, Schmohl J, Kraemer D, Schmid C, Rank A, Schmetzer HM (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 227
Article Number: 152237
Journal Issue: 4
DOI: 10.1016/j.imbio.2022.152237
Abstract
The blastmodulatory Kit-M, composed of granulocyte-macrophage colony-stimulating-factor (GM-CSF) and Prostaglandin E1 (PGE1), is known to convert myeloid leukaemic blasts (from AML patients) into leukaemia derived dendritic cells (DCleu), which activate immunoreactive cells to gain antileukemic/leukaemia-specific activity. In this study we had a special focus on the influence of Kit-M treated, DC/DCleu containing patients'whole blood (WB, n = 16) on the provision of immunosuppressive regulatory T-cells. We could confirm that Kit-M significantly increased frequencies of (mature) dendritic cells (DC) and DCleu from leukemic whole blood (WB) without induction of blast proliferation. After mixed lymphocyte culture (MLC) with patients’ T-cells we confirmed that DCleu mediated leukemia-specific responses- going along with activated and leukemia-specific T- and NK-cells in an intracellular cytokine staining assay (ICS) and a degranulation assay (Deg)- resulted in an increased anti-leukemic cytotoxicity (Cytotoxicity Fluorolysis Assay = CTX). We could demonstrate that (leukemia-specific) CD4+ and CD8+ regulatory T-cell population (Treg) decreased significantly after MLC compared to controls. We found significant positive correlations of leukemia-specific CD3+CD4+ cells with frequencies of (mature) DCleu. Achieved anti-leukemic cytotoxicity correlated significantly positive with leukemia-specific CD3+CD8+ cells and significantly negatively with (leukemia-specific) Treg. In summary we demonstrate that immunesuppressive (leukemia-specific) regulatory T-cells are significantly downregulated after Kit-M triggered MLC- going along with a (reinstalled) antileukemic reactivity of the immune system (as demonstrated with functional assays ICS, Deg, CTX).
Involved external institutions
St Josefs-Hospital
Germany (DE)
Klinikum der Universität München
Germany (DE)
Universitätsklinikum Augsburg
Germany (DE)
Diakonie-Klinikum Stuttgart Diakonissenkrankenhaus und Paulinenhilfe
Germany (DE)
Germany (DE)
Klinikum der Universität München
Germany (DE)
Universitätsklinikum Augsburg
Germany (DE)
Diakonie-Klinikum Stuttgart Diakonissenkrankenhaus und Paulinenhilfe
Germany (DE)
How to cite
APA:
Pepeldjiyska, E., Li, L., Gao, J., Seidel, C.L., Blasi, C., Özkaya, E.,... Schmetzer, H.M. (2022). Leukemia derived dendritic cell (DCleu) mediated immune response goes along with reduced (leukemia-specific) regulatory T-cells. Immunobiology, 227(4). https://doi.org/10.1016/j.imbio.2022.152237
MLA:
Pepeldjiyska, Elena, et al. "Leukemia derived dendritic cell (DCleu) mediated immune response goes along with reduced (leukemia-specific) regulatory T-cells." Immunobiology 227.4 (2022).
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