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CLL-cell-mediated MDSC induction by exosomal miR-155 transfer is disrupted by vitamin D

Leukemia volume 31, pages 985–988 (2017)Cite this article

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B-cell-derived chronic lymphocytic leukemia (CLL) is characterized by immune defects that prevent an efficient anti-tumor response. Both lymphoid and myeloid cells of CLL patients display alterations. Recent data suggest an accumulation of CD14+ monocytes with aberrantly low levels of HLA-DR associated with disease progression.1 These CD14+HLA-DRlow cells belong to the population of myeloid-derived suppressor cells (MDSCs). Increasing evidence highlights the key role of MDSCs within immune suppressive networks found in cancers.2 CLL-MDSCs suppress T-cell responses in an indoleamine-2,3-dioxygenase (IDO)-dependent fashion. Malignant cells (including CLL-cells) hold MDSC-inducing capacities. However, the underlying mechanisms leading to a CLL-triggered reprogramming of regular monocytes into MDSCs remain unclear.

Nowadays, extracellular vesicles such as exosomes are emerging as an important mediator of the cancer cell’s communication with its environment. Exosomes represent small membrane vesicles (30 and 100 nm in diameter) of endocytic origin.3 Malignant cells have been shown to release high levels of exosomes. In fact, exosome plasma concentrations are higher in CLL patients compared with healthy controls, with their secretion being triggered by B-cell receptor signalling.4 CLL-cell-derived microvesicles are incorporated in bone marrow-derived mesenchymal stromal cells and elicit inflammatory activation and transformation into cancer-associated fibroblasts.5

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Acknowledgements

HB was supported by the Angelika and Helmut Trunk Foundation and the Erich and Gertrud Roggenbuck Foundation. DM was supported by IZKF Erlangen, Deutsche Krebshilfe (Max-Eder Junior Research Group), European Hematology Association (EHA) and José Carreras Leukemia Foundation. This work was also supported by grants from the Johannes und Frieda Marohn Foundation.

Author contributions

HB designed the study, analyzed the data and wrote the manuscript. MB, MQ, SJ, LB and RJ performed research and analyzed the data. AM helped in designing the study. DM designed the study, analyzed the data and wrote the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Erlangen, Germany

    H Bruns, M Böttcher, M Qorraj, S Jitschin, L Busch, R Jitschin, A Mackensen & D Mougiakakos

  2. Department of Dermatology, University of Cologne, Cologne, Germany

    M Fabri

  3. Department of Dermatology, University of Erlangen-Nuremberg, Erlangen, Germany

    J Dindorf

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  1. H Bruns
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Correspondence to H Bruns.

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Bruns, H., Böttcher, M., Qorraj, M. et al. CLL-cell-mediated MDSC induction by exosomal miR-155 transfer is disrupted by vitamin D. Leukemia 31, 985–988 (2017). https://doi.org/10.1038/leu.2016.378

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