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

Zarobkiewicz, Michał K.; Kowalska, Wioleta; Chocholska, Sylwia; Tomczak, Waldemar; Szymańska, Agata; Morawska, Izabela; Wojciechowska, Agnieszka

doi:10.3390/cancers12092614

Cited by 21 publications

(21 citation statements)

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“…Sorted CD14 + CD16 − SLAN, CD14 + CD16 + SLAN − and CD14 dim CD16 + SLAN + monocytes were analyzed for TNF, IL-12 and IL-10 mRNA expression in 20 randomly selected CLL patients’ samples. The Quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR) method was performed as previously described [ 27 ]. All molecular tests were based on TaqMan Gene Expression Assays (Thermo Fisher Scientific, Applied Biosystems, Inc., Waltham, MA, USA) using the following assays: Hs00174128_m1 probe for TNF-alpha, Hs01073447_m1 probe for IL-12A and Hs00961622_m1 probe for IL10.…”

Section: Methodsmentioning

confidence: 99%

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Kowalska

Zarobkiewicz

Tomczak

et al. 2022

IJMS

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Monocytes are one of the least studied immune cells with a potentially important role in the pathogenesis of chronic lymphocytic leukemia (CLL). Nevertheless, data regarding the role of subpopulations of monocytes in the CLL microenvironment are still limited. For the very first time, this study presents an assessment of monocyte subsets divided according to SLAN and CD16 expression in CLL patients. The study involved 70 freshly diagnosed CLL patients and 35 healthy donors. Using flow cytometry, monocyte subpopulations were assessed among PBMCs. CD14+ monocytes can be divided into: “classical” (CD14+CD16−SLAN−), “intermediate” (CD14+CD16+SLAN−) and “non-classical” (CD14dimCD16+SLAN+). In our study, we noted an increased percentage of non-classical monocytes with intracellular expression of TNF and IL-12. On the other hand, among the intermediate monocytes, a significantly higher percentage of cells synthesizing anti-inflammatory IL-10 was detected. The percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 decreased with the stage of CLL and inversely correlated with the expression of the prognostic factors ZAP-70 and CD38. Moreover, the percentage of CD14dimCD16+SLAN+ monocytes producing TNF and IL-12 was lower in CLL patients requiring treatment. This may indicate the beneficial effect of non-classical monocytes on the anti-tumor response.

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Section: Methodsmentioning

confidence: 99%

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Kowalska

Zarobkiewicz

Tomczak

et al. 2022

IJMS

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“…Purified CD14+Tie2+ and CD14+Tie2- fractions were analyzed for IL-10 and VEGF mRNA expression by quantitative RT-PCR, according to the method described previously [ 20 ]. All molecular tests were based on TaqMan Gene Expression Assays (Thermo Fisher Scientific, Applied Biosystems, Inc., Waltham, MA, USA)—assay ID for IL-10 was Hs00961622_m1 and, for VEGF Hs00998133_m1, used with TaqMan Gene Expression Master Mix (Cat No.…”

Section: Methodsmentioning

confidence: 99%

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients

Woś

Chocholska

Kowalska

et al. 2021

Cancers

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Tie2-expressing monocytes (TEMs) are associated with tumor progression and metastasis. This unique subset of monocytes has been identified as a potential prognostic marker in several solid tumors. However, TEMs remain poorly characterized in hematological cancers, including chronic lymphocytic leukemia (CLL). This study analyzed, for the first time, the clinical significance of TEM population in CLL patients. Flow cytometry analysis of TEMs (defined as CD14+CD16+Tie2+ cells) was performed at the time of diagnosis on peripheral blood mononuclear cells from 104 untreated CLL patients. Our results revealed an expansion of circulating TEM in CLL patients. These monocytes express high levels of VEGF and suppressive IL-10. A high percentage of TEM was associated closely with unfavorable prognostic markers (ZAP-70, CD38, 17p and 11q deletion, and IGHV mutational status). Moreover, increased percentages of circulating TEMs were significantly higher in patients not responding to the first-line therapy as compared to responding patients, suggesting its potential predictive value. High TEM percentage was also correlated with shorter overall survival (OS) and shorter time to treatment (TTT). Importantly, based on multivariate Cox regression analysis, TEM percentage was an independent predictor for TTT. Thus, we can suggest the adverse role of TEMs in CLL.

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“…A slightly different approach, with the lymphocyte/monocyte ratio, gives the same results in HL ( 23 , 28 , 29 ) and DLBCL ( 30 ). This could be linked to an increase in monocytic myeloid derived suppressor cells (M-MDSC), as it has been suggested in DLBCL ( 20 , 31 ) and CLL, in which M-MDSC levels correlate with response to treatment ( 32 – 35 ). Concerning the granulocytic lineage, polymorphonuclear MDSC (PMN-MDSC) have been proposed as a marker of poor prognosis in DLBCL ( 36 ), but other works did not find any association between PMN-MDSC and DLBCL prognosis ( 31 , 37 ).…”

Section: Introductionmentioning

confidence: 94%

Circulating Myeloid Regulatory Cells: Promising Biomarkers in B-Cell Lymphomas

et al. 2021

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The monocyte/macrophage lineage has been shown to be involved in the promotion of a protumoral tumor microenvironment and resistance to treatment in B cell lymphomas. However, it is still poorly described at the single cell level, and tissue samples are not easily accessible. Thus, a detailed analysis of the circulating myeloid cell compartment in the different B lymphomas is needed to better understand the mechanisms of resistance to treatment and identify at risk patients. In this Perspective, we review current knowledge on the phenotypic and functional description of the circulating monocytic lineage in B cell lymphomas and provide first insights into the heterogeneity of these cell populations in health and lymphoma, using mass cytometry. Indeed, the monocytic compartment is a continuum more than distinct subpopulations, as demonstrated by our high-resolution approach, explaining the sometimes confusing and contradictory conclusions on the prognostic impact of the different populations, including monocytes and monocytic myeloid derived suppressor cells (M-MDSC). By identifying S100A9high monocytic cells as a potential biomarker in diffuse large B cell lymphoma (DLBCL) in this proof-of-concept preliminary study including a limited number of samples, we underline the potential of circulating myeloid regulatory cells as diagnostic and prognostic biomarkers in B-cell lymphomas.

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

Cited by 21 publications

References 50 publications

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Reduced Percentage of CD14dimCD16+SLAN+ Monocytes Producing TNF and IL-12 as an Immunological Sign of CLL Progression

Prognostic Value of Tie2-Expressing Monocytes in Chronic Lymphocytic Leukemia Patients

Circulating Myeloid Regulatory Cells: Promising Biomarkers in B-Cell Lymphomas

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