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. 2021 May;226(3):152088.
doi: 10.1016/j.imbio.2021.152088. Epub 2021 Mar 20.

Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in 'DC-culture-media' shifts correlations of released chemokines with antileukemic T-cell reactions

M Merle  1 , D Fischbacher  1 , A Liepert  1 , C Grabrucker  1 , T Kroell  1 , A Kremser  1 , J Dreyssig  1 , M Freudenreich  1 , F Schuster  2 , A Borkhardt  2 , D Kraemer  3 , C-H Koehne  3 , H J Kolb  4 , C Schmid  5 , H M Schmetzer  6
Affiliations

Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in 'DC-culture-media' shifts correlations of released chemokines with antileukemic T-cell reactions

M Merle et al. Immunobiology. 2021 May.

Abstract

Dendritic cells (DC) and T-cells are mediators of CTL-responses. Autologous (from patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS)) or allogeneic (donor)-T-cells stimulated by DCleu, gain an efficient lysis of naive blasts, although not in every case. CXCL8, -9, -10, CCL2, -5 and Interleukin (IL-12) were quantified by Cytometric Bead Array (CBA) in supernatants from 5 DC-generating methods and correlated with AML-/MDS-patients' serum-values, DC-/T-cell-interactions/antileukemic T-cell-reactions after mixed lymphocyte culture (MLC) and patients' clinical course. The blast-lytic activity of T-cells stimulated with DC or mononuclear cells (MNC) was quantified in a cytotoxicity assay. Despite great variations of chemokine-levels, correlations with post-stimulation (after stimulating T-cells with DC in MLC) improved antileukemic T-cell activity were seen: higher released chemokine-values correlated with improved T-cells' antileukemic activity (compared to stimulation with blast-containing MNC) - whereas with respect to the corresponding serum values higher CXCL8-, -9-, and -10- but lower CCL5- and -2-release correlated with improved antileukemic activity of DC-stimulated (vs. blast-stimulated) T-cells. In DC-culture supernatants higher chemokine-values correlated with post-stimulation improved antileukemic T-cell reactivity, whereas higher serum-values of CXCL8, -9, and -10 but lower serum-values of CCL5 and -2 correlated with post-stimulation improved antileukemic T-cell-reactivity. In a context of 'DC'-stimulation (vs serum) this might point to a change of (CCL5 and -2-associated) functionality from a more 'inflammatory' or 'tumor-promoting' to a more 'antitumor'-reactive functionality. This knowledge could contribute to develop immune-modifying strategies that promote antileukemic (adaptive) immune-responses.

Keywords: Acute myeloid leukemia; Chemokines; Dendritic cells; Immunotherapy; T-cells.

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