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Vogt, V.* ; Walcher, T.* ; Ansprenger, C.* ; Braeu, M. ; Kroell, T.* ; Kraemer, D.M.* ; Köhne, C.H.* ; Hausmann, A.* ; Buhmann, R. ; Tischer, J. ; Schmetzer, H.M.

Profiles of activation, differentiation-markers, or β-integrins on T cells contribute to predict T cells' antileukemic responses after stimulation with leukemia-derived dendritic cells.

J. Immunother. 37, 331-347 (2014)

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

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Stem cell transplantations and donor lymphocyte infusions are promising immunotherapies to cure acute myeloid leukemia (AML). Leukemia-derived dendritic cells are known to improve antileukemic functionality of T cells. We evaluated the composition and development of distinct T-cell subtypes in AML patients (n=12) compared with healthy probands (n=5) before and during stimulation with leukemia-derived dendritic cells-containing DC (DC) or blast-containing mononuclear cells (MNC) in 0-7 days mixed lymphocyte cultures (MLC) by flow cytometry. AML patients' T-cell subgroups were correlated with antileukemic functionality before and after DC/MNC stimulation by functional fluorolysis assays. (1) Unstimulated T cells from AML patients presented with significantly lower proportions of activated, T+ cm, CD137+, and β-integrin T cells, and significantly higher proportions of T naive and Teff compared with healthy probands. (2) After 7 days of DC or MNC stimulation, T-cell profiles were characterized by (significantly) increased proportions of activated T cells with effector function and significantly decreased proportions of β-integrin+m T cells. (3) Antileukemic cytotoxicity was achieved in 40% of T cells after MNC stimulation compared with 64% after DC stimulation. Antileukemic activity after DC stimulation but not after MNC stimulation correlated with higher proportions of Tcm and Tnaive before stimulation, as well as with significantly higher proportions of activated and β-integrin+T cells. Furthermore, cutoff values for defined T-cell activation/differentiation markers and β-integrin+T cells could be defined, allowing a prediction of antileukemic reactivity. We could demonstrate the potential of the composition of unstimulated/DC-stimulated T cells for the lysis of AML blasts. Especially, AML patients with high numbers of Tnaive and T cm could benefit from DC stimulation; proportions of activated and β-integrin+ T cells correlated with increased antileukemic functionality and could serve to predict T cells' reactivity during stimulation. Refined analyses in the context of responses to immunotherapies are required. Copyright © 2014 by Lippincott Williams & Wilkins.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Aml ; Dendritic Cells ; T-cell Differentiation ; T-cell Memory ; T-effector Cells ; β-integrins; Acute Myeloid-leukemia; Central Memory; In-vivo; Risk-factors; Effector; Transplantation; Lymphocytes; Generation; Expression; Subsets

ISSN (print) / ISBN 1524-9557

e-ISSN 1537-4513

Journal Journal of Immunotherapy

Quellenangaben Volume: 37, Issue: 6, Pages: 331-347

Publisher Lippincott Williams & Wilkins

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Molecular Immunology (IMI)
CCG Hematopoetic Cell Transplants (IMI-KHZ)