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Acute myeloid leukemia cells fail to activate native human dendritic cells: a potential mechanism of immune evasion

Leukemia volume 24, pages 1965–1967 (2010)Cite this article

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Natural killer (NK) cells and T cells are considered be important in the immunosurveillance of acute myeloid leukemia (AML).1 NK cells as potent effectors of innate immunity possess efficient immunomodulatory and cytotoxic properties, which essentially contribute to the elimination of AML cells. CD8+ cytotoxic T cells (CTLs) and CD4+ T cells represent important effectors in adaptive antitumor immunity. CD8+ CTLs are able to recognize and destroy AML cells. CD4+ T cells enhance the capacity of dendritic cells (DCs) to induce CD8+ CTLs by the interaction between CD40 on DCs and CD40 ligand on activated CD4+ T cells. In addition, they provide help for the maintenance and expansion of CD8+ CTLs by secreting cytokines such as interleukin (IL)-2 and are able to eradicate tumor cells directly. Owing to their various antitumor effects, NK cells and T cells emerged as promising candidates for immunotherapeutic strategies in AML therapy.1 However, recent studies revealed that human AML cells can efficiently evade the control of these potent immune effector cells. Thus, it has been shown that AML cells downregulate the entire mismatched human leukocyte antigen haplotype to avoid powerful antileukemia effects mediated by donor T cells after haploidentical stem cell transplantation.2 In addition, it has been shown that cytokine production and cytotoxic activity of NK cells can be markedly impaired by AML cells. This effect is mediated by the interaction between the glucocorticoid-induced tumor necrosis factor (TNF) receptor-related protein on NK cells and its AML cell membrane-associated or -soluble ligand.3 More recently, Baessler et al.4 reported that the interaction of CD137 ligand on AML cells and CD137 on NK cells can also efficiently inhibit NK-cell-mediated antitumor effects.

Whereas these reports offer potential explanations how AML cells can evade the control of NK cells and T cells, little is known about the impact of primary AML cells on native human DCs, which have a major role in the activation of innate and adaptive antitumor responses. Recently, we defined 6-sulfo LacNAc (slan)DCs (formerly termed M-DC8+ DCs) as a major subpopulation of proinflammatory myeloid human blood DCs, which mainly differ from other blood DC subsets by their selective phenotype (6-sulfo LacNAc+, CD1c−, CD11c+, CD14−, CD16+, CD45RA+, C5aR+).5, 6 Functional data revealed that slanDCs can mediate tumor-directed cytotoxicity and efficiently activate tumor-reactive NK cells and CD8+ CTLs.7 To get novel insights into the impact of primary human AML cells on native human DCs, we investigated the capacity of AML cells to modulate the secretion of TNF-α and IL-12 by slanDCs. In previous studies, we have shown that activated slanDCs produce large amounts of TNF-α, which essentially contributes to their tumor-directed cytotoxicity.5, 7 In addition, we have shown that activated slanDCs are principal producers of IL-12, which favors the differentiation of naive CD4+ T cells into Th1 cells and is important in NK cell activation.6, 8

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Acknowledgements

The technical assistance of Bärbel Löbel, Karin Günther, Jule Kriegel and Anne Seltmann (all from the Institute of Immunology) is greatly appreciated. We also thank Silke Soucek and Michael Kramer for providing the characteristics of the AML cells. This work was supported by grants from the Deutsche Forschungsgemeinschaft to MB and GE (SFB655, project B2 and B7) and from the Medical Faculty, Technical University of Dresden to RW.

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Authors and Affiliations

  1. Institute of Immunology, Medical Faculty, Technical University of Dresden, Dresden, Germany

    R Wehner, P Schumacher, M Bachmann & M Schmitz

  2. Department of Medicine I, University Hospital of Dresden, Dresden, Germany

    M Bornhäuser & G Ehninger

  3. Department of Dermatology, University Hospital of Heidelberg, Heidelberg, Germany

    K Schäkel

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  1. R Wehner
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  2. P Schumacher
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Correspondence to M Schmitz.

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Wehner, R., Schumacher, P., Bornhäuser, M. et al. Acute myeloid leukemia cells fail to activate native human dendritic cells: a potential mechanism of immune evasion. Leukemia 24, 1965–1967 (2010). https://doi.org/10.1038/leu.2010.189

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