NOX2-dependent immunosuppression in chronic myelomonocytic leukemia

Johan Aurelius, Alexander Hallner, Olle Werlenius, Rebecca Riise, Lars Möllgård, Mats Brune, Markus Hansson, Anna Martner, Fredrik B Thorén, Kristoffer Hellstrand

    Research output: Contribution to journalArticlepeer-review


    Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloid cell NADPH oxidase-2 (NOX2). The dominant population of primary human CMML cells was found to express membrane-bound NOX2 and to release ROS, which, in turn, triggered extensive PARP-1-dependent cell death in cocultured NK cells, CD8(+) T effector memory cells, and CD8(+) T effector cells. Inhibitors of ROS formation and scavengers of extracellular ROS prevented CMML cell-induced lymphocyte death and facilitated NK cell degranulation toward Ab-coated, primary CMML cells. In patients with CMML, elevation of immature cell counts (CD34(+)) in blood was associated with reduced expression of several NK cell-activating receptors. We propose that CMML cells may use extracellular ROS as a targetable mechanism of immune escape.

    Original languageEnglish
    Pages (from-to)459-466
    JournalJournal of Leukocyte Biology
    Issue number2
    Publication statusPublished - 2017 Aug

    Subject classification (UKÄ)

    • Hematology
    • Cancer and Oncology


    • Cell Separation
    • Flow Cytometry
    • Humans
    • Immunophenotyping
    • Leukemia, Myelomonocytic, Chronic
    • Membrane Glycoproteins
    • Microscopy, Confocal
    • Myeloid Cells
    • NADPH Oxidase
    • Reactive Oxygen Species
    • Tumor Escape
    • Journal Article


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