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

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2614
Author(s):  
Michał Zarobkiewicz ◽  
Wioleta Kowalska ◽  
Sylwia Chocholska ◽  
Waldemar Tomczak ◽  
Agata Szymańska ◽  
...  

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

2020 ◽  
Vol 11 ◽  
Author(s):  
Lennart Achmus ◽  
Johanna Ruhnau ◽  
Sascha Grothe ◽  
Bettina von Sarnowski ◽  
Barbara M. Bröker ◽  
...  

Background: Stroke patients are at risk of acquiring secondary infections due to stroke-induced immune suppression (SIIS). Immunosuppressive cells comprise myeloid-derived suppressor cells (MDSCs) and immunosuppressive interleukin 10 (IL-10)-producing monocytes. MDSCs represent a small but heterogeneous population of monocytic, polymorphonuclear (or granulocytic), and early progenitor cells (“early” MDSC), which can expand extensively in pathophysiological conditions. MDSCs have been shown to exert strong immune-suppressive effects. The role of IL-10-producing immunosuppressive monocytes after stroke has not been investigated, but monocytes are impaired in oxidative burst and downregulate human leukocyte antigen—DR isotype (HLA-DR) on the cell surface.Objectives: The objective of this work was to investigate the regulation and function of MDSCs as well as the immunosuppressive IL-10-producing monocytes in experimental and human stroke.Methods: This longitudinal, monocentric, non-interventional prospective explorative study used multicolor flow cytometry to identify MDSC subpopulations and IL-10 expression in monocytes in the peripheral blood of 19 healthy controls and 27 patients on days 1, 3, and 5 post-stroke. Quantification of intracellular STAT3p and Arginase-1 by geometric mean fluorescence intensity was used to assess the functionality of MDSCs. In experimental stroke induced by electrocoagulation in middle-aged mice, monocytic (CD11b+Ly6G−Ly6Chigh) and polymorphonuclear (CD11b+Ly6G+Ly6Clow) MDSCs in the spleen were analyzed by flow cytometry.Results: Compared to the controls, stroke patients showed a relative increase in monocytic MDSCs (percentage of CD11b+ cells) in whole blood without evidence for an altered function. The other MDSC subgroups did not differ from the control. Also, in experimental stroke, monocytic, and in addition, polymorphonuclear MDSCs were increased. The numbers of IL-10-positive monocytes did not differ between the patients and controls. However, we provide a new insight into monocytic function post-stroke since we can report that a differential regulation of HLA-DR and PD-L1 was found depending on the IL-10 production of monocytes. IL-10-positive monocytes are more activated post-stroke, as indicated by their increased HLA-DR expression.Conclusions: MDSC and IL-10+ monocytes can induce immunosuppression within days after stroke.


2003 ◽  
Vol 120 (6) ◽  
pp. 1017-1025 ◽  
Author(s):  
Eric D. Hsi ◽  
Kenneth J. Kopecky ◽  
Frederick R. Appelbaum ◽  
David Boldt ◽  
Tom Frey ◽  
...  

Urology ◽  
2003 ◽  
Vol 61 (5) ◽  
pp. 1072-1077 ◽  
Author(s):  
Akira Miyajima ◽  
Tomohiko Asano ◽  
Kaori Seta ◽  
Takako Asano ◽  
Narihiko Kakoi ◽  
...  

Methods ◽  
2018 ◽  
Vol 134-135 ◽  
pp. 32-40 ◽  
Author(s):  
Henry Hui ◽  
Kathryn A. Fuller ◽  
Hun Chuah ◽  
James Liang ◽  
Hasib Sidiqi ◽  
...  

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