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

• Published in: Immunobiology (1979) 2021-05, Vol.226 (3), p.152088-152088, Article 152088
• Main Authors: 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.M.
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Chemokines; Chemokines - biosynthesis; Chemokines - blood; Cytotoxicity, Immunologic; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Humans; Immunity; Immunotherapy; Leukemia, Myeloid, Acute - diagnosis; Leukemia, Myeloid, Acute - etiology; Leukemia, Myeloid, Acute - metabolism; Lymphocyte Activation - immunology; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - etiology; Myelodysplastic Syndromes - metabolism; T-cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; T-Lymphocytes - pathology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - pathology
• ISSN: 0171-2985; 1878-3279
• DOI: 10.1016/j.imbio.2021.152088

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.