Myeloid-derived suppressor cell heterogeneity and subset definition

Peranzoni, Elisa; Zilio, Serena; Marigo, Ilaria; Dolcetti, Luigi; Zanovello, Paola; Mandruzzato, Susanna; Bronte, Vincenzo

doi:10.1016/j.coi.2010.01.021

Cited by 582 publications

(586 citation statements)

References 48 publications

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“…It has been reported that a heterogeneous population of immature myeloid cells known as MDSCs can modulate NK [1][2][3] and T cell function [4][5][6][7] and may contribute to the immune escape of tumors. 6,8 In fact, the elimination of MDSCs by chemotherapy in some models resulted in the augmentation of both the proportion and function of cytotoxic T cells. [9][10][11] MDSCs have been intensively studied in spleen 7,11,12 and within a tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

et al. 2015

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TNFa, tumor necrosis factor a; VEGF, vascular endothelial growth factor.Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSCs in non-Hodgkin lymphoma (NHL) patients was increased and inversely correlated with that of NK cells, but not that of T cells. To investigate the regulation of MDSC subsets by NK cells, we used an EL4 murine lymphoma model and found the non-monocytic and non-granulocytic MDSC subset, i.e., Gr1 C CD11b C Ly6G med Ly6C med MDSC, is increased after NK cell depletion. The MDSC population that expresses MHC class II, CD80, CD124, and CCR2 is regulated mainly by CD27 C CD11b C NK cells. In addition, this MDSC subset produces some immunosuppressive cytokines, including IL-10 but not nitric oxide (NO) or arginase. We also examined two subsets of MDSCs (CD14 C HLA-DR ¡ and CD14 ¡ HLA-DR ¡ MDSC) in NHL patients and found that higher IL-10-producing CD14 C HLA-DR ¡ MDSC subset can be seen in lymphoma patients with reduced NK cell frequency in peripheral blood. Our analyses of MDSCs in this study may enable a better understanding of how MDSCs manipulate the tumor microenvironment and are regulated by NK cells in patients with lymphoma.

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Section: Introductionmentioning

confidence: 99%

Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

et al. 2015

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“…25 y ago (7). MDSCs are a heterogeneous population of myeloid cells made up of monocytes/macrophages, granulocytes, and dendritic cells that are dramatically increased in the blood of cancer patients and in tumor-bearing mice (8)(9)(10). In mice, MDSCs are commonly characterized as CD11b + Gr-1 + .…”

mentioning

confidence: 99%

“…MDSCs also suppress immune effector function by generation of Tregs (11). Modification of the behavior of immune cells such as T cells, NK cells, and myeloid cells in the tumor microenvironment may play a key role in tumor development (8)(9)(10)(11)15).…”

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confidence: 99%

Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells

Husain

Huang

Seth

et al. 2013

The Journal of Immunology

627

473

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In this study, we explore the hypothesis that enhanced production of lactate by tumor cells, because of high glycolytic activity, results in inhibition of host immune response to tumor cells. Lactate dehydrogenase-A (LDH-A), responsible for conversion of pyruvate to lactate, is highly expressed in tumor cells. Lentiviral vector–mediated LDH-A short hairpin RNA knockdown Pan02 pancreatic cancer cells injected in C57BL/6 mice developed smaller tumors than mice injected with Pan02 cells. A decrease occurred in the frequency of myeloid-derived suppressor cells (MDSCs) in the spleens of mice carrying LDH-A–depleted tumors. NK cells from LDH-A–depleted tumors had improved cytolytic function. Exogenous lactate increased the frequency of MDSCs generated from mouse bone marrow cells with GM-CSF and IL-6 in vitro. Lactate pretreatment of NK cells in vitro inhibited cytolytic function of both human and mouse NK cells. This reduction of NK cytotoxic activity was accompanied by lower expression of perforin and granzyme in NK cells. The expression of NKp46 was decreased in lactate-treated NK cells. These studies strongly suggest that tumor-derived lactate inhibits NK cell function via direct inhibition of cytolytic function as well as indirectly by increasing the numbers of MDSCs that inhibit NK cytotoxicity. Depletion of glucose levels using a ketogenic diet to lower lactate production by glycolytic tumors resulted in smaller tumors, decreased MDSC frequency, and improved antitumor immune response. These studies provide evidence for an immunosuppressive role of tumor-derived lactate in inhibiting innate immune response against developing tumors via regulation of MDSC and NK cell activity.

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“…Chez la souris, les MDSC sont caracté-risées phénotypiquement par la coexpression des marqueurs membranaires Ly6c/g (aussi appelé Gr1) et CD11b et une morphologie mixte associant des caractéristiques de monocytes mononucléés et de polynucléaires neutrophiles [2]. Ces cellules représentent 20 à 30 % des cellules dans la moelle osseuse, 2 à 4 % de celles de la rate et elles sont absentes des ganglions lymphatiques.…”

Section: Phénotype Et Biologie Des Mdscunclassified