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Chronic lymphocytic leukemia

A novel immunoregulatory function of beta-2-microglobulin as a promoter of myeloid derived suppressor cell induction

Leukemia volume 33, pages 1282–1287 (2019)Cite this article

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Chronic lymphocytic leukemia (CLL) is the leukemia with the highest incidence among adults in the Western world. Monoclonal B-cells expand in the bone marrow, lymphoid organs, and eventually the peripheral blood where they engage in complex heterocellular interactions. Numerous immune defects including (pseudo-)exhausted T-cells have been described in CLL patients. Those alterations do not only favor tumor immune escape but can also be crucial hurdles for immunotherapy [1].

Recent studies report the expansion of (monocytic) myeloid-derived suppressor cells (MDSCs) in CLL [2]. MDSCs are a heterogeneous population of immature phenotype and myeloid origin that expands during inflammation, infection, and cancer, and has the ability to suppress adaptive immunity. MDSCs employ various mechanisms for regulating T-cell responses such as abundant production of reactive oxygen species (ROS) or tryptophan depletion by indoleamine-2,3-dioxygenase (IDO). CD14+ MDSCs express low levels of HLA-DR (HLA-DRlo), are morphologically and phenotypically similar to monocytes [2], and represent one of the best-characterized MDSC subset in humans [3]. MDSC accumulation correlates with the patients’ disease burden while CLL-cells have the ability to elicit reprogramming of conventional monocytes towards CD14+HLA-DRlo MDSCs [2, 4]. One of the underlying mechanisms is exosomal transfer of microRNAs (from CLL- to myeloid cells) with induced MDSCs suppressing T-cells and promoting tolerogenic regulatory T-cells in an IDO-dependent fashion [2, 4]. The clinical relevance of MDSCs in CLL is further supported by observations that the frequency of CD14+HLA-DRlo MDSCs is associated with the time to disease progression [5], whereas elimination of myeloid cells can improve anti-tumor immunity in preclinical CLL models [6].

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Acknowledgements

HB was supported by the Wilhelm Sander Foundation. RJ was supported by the IZKF Erlangen (Projekt J67). DM was supported by the Else Kröner-Fresenius Foundation.

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Authors and Affiliations

  1. Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany

    Heiko Bruns, Simon Jitschin, Sara Gamali, Domenica Saul, Martin Böttcher, Andreas Mackensen, Regina Jitschin & Dimitrios Mougiakakos

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  1. Heiko Bruns
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  7. Regina Jitschin
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  8. Dimitrios Mougiakakos
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Contributions

HB designed the study, analyzed data, and wrote the manuscript. SJ, SG, DS, MB, AM, and RJ analyzed data, and helped writing the manuscript. DM designed the study, analyzed data, and wrote the manuscript.

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Correspondence to Dimitrios Mougiakakos.

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Bruns, H., Jitschin, S., Gamali, S. et al. A novel immunoregulatory function of beta-2-microglobulin as a promoter of myeloid derived suppressor cell induction. Leukemia 33, 1282–1287 (2019). https://doi.org/10.1038/s41375-018-0345-0

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