Journal
IMMUNOBIOLOGY
Volume 227, Issue 4, Pages -Publisher
ELSEVIER GMBH
DOI: 10.1016/j.imbio.2022.152237
Keywords
Leukemia derived DC; Acute myeloid leukaemia; Anti-leukaemic functionality; Leukemia -specific cells; Regulatory T cells
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Funding
- China Scholarship Council (CSC)-international
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This study focused on the influence of Kit-M treated DC/DCleu in the whole blood of leukemia patients on the generation of immunosuppressive regulatory T-cells. The results showed that Kit-M significantly increased the frequency of mature dendritic cells and leukemia-derived dendritic cells, leading to enhanced leukemia-specific immune responses and cytotoxicity against leukemia cells.
The blastmodulatory Kit-M, composed of granulocyte-macrophage colony-stimulating-factor (GM-CSF) and Prostaglandin E1 (PGE(1)), 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 patient-s'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 (T-reg) decreased significantly
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