Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies

Palumbo, Giuseppe A.; Parrinello, Nunziatina Laura; Giallongo, Cesarina; D’Amico, Emanuele; Zanghì, Aurora; Puglisi, Fabrizio; Conticello, Concetta; Chiarenza, Annalisa; Tibullo, Daniele; Raimondo, Francesco Di; Romano, Alessandra

doi:10.3390/ijms20215459

Cited by 26 publications

(28 citation statements)

References 116 publications

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“…In accordance with previous studies [17,23,24], we found an increased frequency of M-MDSC in CLL patients in comparison to healthy controls. M-MDSC are also expanded in the peripheral blood of freshly diagnosed patients with Hodgkin's lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, and other haematological malignancies [18]. Consistent with our study, Liu et al revealed that M-MDSC cells are associated with the CLL clinical stage [25].…”

Section: Discussionsupporting

confidence: 92%

“…Nevertheless, the percentage of M-MDSC in the peripheral blood of various indolent lymphomas (mostly follicular lymphomas) is significantly higher when compared to healthy controls, while being significantly lower than in more aggressive lymphomas [16,17]. In addition, a monocytic subset of MDSC (CD14 + HLA-DR low ) is increased in CLL (chronic lymphocytic leukaemia) patients and has a capacity to inhibit T cell activation, as well as induce Treg via IDO [18]. Concurrently, no difference was observed in mycosis fungoides [19] and Waldenström macroglobulinemia [17].…”

Section: Introductionmentioning

confidence: 99%

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

Zarobkiewicz

Kowalska

Chocholska

et al. 2020

Cancers

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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

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Zarobkiewicz

Kowalska

Chocholska

et al. 2020

Cancers

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“…During tumor microenvironment (TME), MDSCs suppress the host anti-tumor immune response through inhibition of T cell proliferation, cytokine secretion, and recruitment of regulatory T cells in hematological malignancies. In all hematological malignancies, several strategies to target MDSCs could improve immune therapies via multiple mechanisms, such as hampering MDSCs function, promoting MDSCs maturation, and depleting MDSCs [82][83][84]. HMGB1 can facilitate MDSCs differentiation in BM and inhibit the activation of antigen-driven CD4 + and CD8 + T cells.…”

Section: Hmgb1 and The Inflammatory Bone Marrow Microenvironmentmentioning

confidence: 99%

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

et al. 2020

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High mobility group box 1 (HMGB1) is a nonhistone chromatin-associated protein that has been widely reported to play a pivotal role in the pathogenesis of hematopoietic malignancies. As a representative damage-associated molecular pattern (DAMP), HMGB1 normally exists inside cells but can be secreted into the extracellular environment through passive or active release. Extracellular HMGB1 binds with several different receptors and interactors to mediate the proliferation, differentiation, mobilization, and senescence of hematopoietic stem cells (HSCs). HMGB1 is also involved in the formation of the inflammatory bone marrow (BM) microenvironment by activating proinflammatory signaling pathways. Moreover, HMGB1-dependent autophagy induces chemotherapy resistance in leukemia and multiple myeloma. In this review, we systematically summarize the emerging roles of HMGB1 in carcinogenesis, progression, prognosis, and potential clinical applications in different hematopoietic malignancies. In summary, targeting the regulation of HMGB1 activity in HSCs and the BM microenvironment is highly beneficial in the diagnosis and treatment of various hematopoietic malignancies.

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“…The accumulation of MDSCs has been demonstrated in many types of human solid tumors [6]. However, the relevance of this heterogeneous population in hematopoietic malignancies has only recently gained stronger attention [7][8][9][10]. MDSCs are a phenotypically and functionally heterogeneous group of cells.…”

Section: Introductionmentioning

confidence: 99%

“…The leukemic B cells achieve this mainly through the involvement of regulatory T (Treg) cells. In turn, MDSCs release IL-10 and TGF-b to exert their suppressive function by Tregs [8,20]. The origin of M-MDSC is unknown.…”

Section: Introductionmentioning

confidence: 99%

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

Kowalska

2020

Folia Histochem Cytobiol.

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Introduction. Myeloid derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment. The accumulation of MDSCs has been demonstrated in many types of human solid tumors. However, the relevance of this heterogeneous population in hematopoietic malignancies has only recently gained stronger attention. MDSCs are a phenotypically and functionally heterogeneous group of cells. The results of recent studies indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) affects a monocytic MDSC (M-MDSC) subpopulation. This study aimed to analyze the frequency of M-MDSCs with intracellular IL-10 and TGF-b1 expression in newly diagnosed CLL patients. We investigated the potential role of M-MDSCs in CLL by analyzing the level of IL-10 and TGF-b1 expression in circulating M-MDSCs in correlation with clinical and laboratory parameters characterizing disease activity and patients' immune status. Material and methods. Seventy CLL patients and 17 age-matched healthy volunteers were included in this study. Flow cytometric detection of Mo-MDSCs (CD14 + CD11b + CD15-HLA-DR-/low) with intracellular IL-10 and TGF-b1 expression was done. Results. We found a significantly higher median percentage of M-MDSC with IL-10 or TGF-b1 expression in CLL patients than in healthy volunteers. The percentage of M-MDSC with intracellular IL-10 or TGF-b1 expression was significantly lower in CLL patients at stage 0 as compared to the stages I/II and III/IV according to Rai stages. The percentage of M-MDSC with intracellular TGF-b1 expression was significantly higher in ZAP-70-positive and CD38-positive patients compared with ZAP-70-negative and group of CD38-negative ones. There was also a significantly higher percentage of M-MDSC positive for intracellular TGF-b expression in patients carrying the 11q22.3 and/or the 17p13.1 deletion than in patients without these genetic aberrations. The percentage of M-MDSC IL-10-positive and M-MDSC TGF-b1-positive measured at the time of diagnosis was higher in patients requiring therapy as compared to patients without treatment during the observation period. Conclusion. In conclusion, we have shown that an increased percentage of M-MDSC cells producing IL-10 and TGF-b1 in CLL patients may be associated with the suppression of the immune response against CLL. It can be assumed that the increased percentage of M-MDSC with an intracellular expression of IL-10 and TGF-b1 may be used in the future as the factor defining the group of patients with shorter time to onset of treatment.

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Monocytic Myeloid Derived Suppressor Cells in Hematological Malignancies

Cited by 26 publications

References 116 publications

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

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

High mobility group box 1 (HMGB1): a pivotal regulator of hematopoietic malignancies

Monocytic MDSC as a source of immunosuppressive cytokines in chronic lymphocytic leukemia (CLL) microenvironment

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