High M-MDSC Percentage as a Negative Prognostic Factor in Chronic Lymphocytic Leukaemia

SIMPLE SUMMARY: Chronic lymphocytic leukaemia (CLL) is a malignancy of mature B cells. Tumour microenvironment is important for survival and proliferation of malignant cells. In the current study, we investigated the potential role of circulating monocytic myeloid-derived suppressor cells (M-MDSC) in CLL. We have observed an increased percentage of M-MDSC cells in CLL patients. Moreover, we have observed a close association with unfavourable prognostic markers, which suggests a potential role of M-MDSC as a prognostic factor in CLL. We have established an association between a high M-MDSC percentage on the one side and shorter time-to-treatment and overall survival on the other. Therefore, we strongly suggest to use M-MDSC percentage as another prognostic factor. ABSTRACT: In the current study, we analysed the role and prognostic value of myeloid-derived suppressor cells (MDSC) in chronic lymphocytic leukaemia (CLL). The frequency of circulating monocytic MDSC (M-MDSC; defined as CD14(+)CD11b(+)CD15(-)HLA-DR(-/low) cells) was assessed in correlation with clinical and laboratory parameters characterising the disease activity and patient immune status. Samples of peripheral blood from untreated CLL patients and healthy volunteers were stained with monoclonal antibodies for flow cytometry analysis. CLL patients with M-MDSC percentages above 9.35% (according to the receiver operating characteristic (ROC) analysis) had a shorter time-to-treatment and shorter survival time than the group with a lower percentage of M-MDSC. The M-MDSC percentage was higher in patients with adverse prognostic factors (i.e., 17p and 11q deletion and CD38 and ZAP-70 expression). A high M-MDSC percentage was linked to significantly lower expression of the CD3ζ in T cells. Furthermore, an analysis of immune regulatory molecules (arginase 1 (ARG1), nitric oxide synthase (NOS2), indoleamine 2,3-dioxygenase (IDO), transforming growth factor beta (TGF-β), and interleukin (IL)-10) was performed. By the means of flow cytometry and RT-qPCR, we showed an overexpression of three of them in M-MDSC of CLL patients. M-MDSC cells seem to be an important factor in the immunosuppressive microenvironment of CLL and seem to be a good and novel prognostic factor