High M-MDSC Percentage as a Negative Prognostic Factor in Chronic Lymphocytic Leukaemia.
Michał Konrad ZarobkiewiczAgnieszka Bojarska-JunakSylwia ChocholskaWaldemar TomczakAgata SzymańskaIzabela Morawska-MichalskaAgnieszka WojciechowskaAgnieszka A Bojarska-JunakPublished in: Cancers (2020)
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.
Keyphrases
- prognostic factors
- flow cytometry
- induced apoptosis
- transforming growth factor
- nitric oxide synthase
- cell cycle arrest
- disease activity
- chronic lymphocytic leukemia
- poor prognosis
- peripheral blood
- nitric oxide
- end stage renal disease
- rheumatoid arthritis
- systemic lupus erythematosus
- stem cells
- epithelial mesenchymal transition
- emergency department
- newly diagnosed
- endoplasmic reticulum stress
- rheumatoid arthritis patients
- cell death
- transcription factor
- cell proliferation
- chronic kidney disease
- nk cells
- binding protein
- oxidative stress
- peritoneal dialysis
- patient reported outcomes
- smoking cessation
- data analysis