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Merle, M.* ; Fischbacher, D.* ; Liepert, A.* ; Grabrucker, C.* ; Kroell, T.* ; Kremser, A.* ; Dreyssig, J.* ; Freudenreich, M.* ; Schuster, F.* ; Borkhardt, A.* ; Kraemer, D.* ; Koehne, C.H.* ; Kolb, H.J. ; Schmid, C.* ; Schmetzer, H.

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

Immunobiology 226:152088 (2021)

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Open Access Green as soon as Postprint is submitted to ZB.

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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 DC_leu, 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Acute Myeloid Leukemia ; Chemokines ; Dendritic Cells ; Immunotherapy ; T-cells; Acute Myeloid-leukemia; Antigen-presenting Cells; Serum-free Generation; Ex-vivo; Myelodysplastic Syndrome; Protective Immunity; Tumor-cells; Transplantation; Polarization; Maturation

ISSN (print) / ISBN 0171-2985

e-ISSN 1878-3279

Journal Immunobiology : Experimental and Clinical

Quellenangaben Volume: 226, Issue: 3, Article Number: 152088

Publisher Urban & Fischer

Publishing Place Hackerbrucke 6, 80335 Munich, Germany

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CCG Immunotherapy (KKG-KIT)