Expansion of Monocytic Myeloid-Derived Suppressor Cells Dampens T Cell Function in HIV-1-Seropositive Individuals

Qin, Aiping; Cai, Weiping; Pan, Ting; Wu, Kang; Yang, Qiong; Wang, Na; Liu, Yufeng; Yan, Dehong; Hu, Fengyu; Guo, Peng; Chen, Xiaoping; Chen, Ling; Zhang, Hui; Tang, Xiaoping; Zhou, Jie

doi:10.1128/jvi.01759-12

Cited by 142 publications

(232 citation statements)

References 42 publications

(64 reference statements)

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“…Vollbrecht et al (2012) showed that chronically HIV-infected HAART-naive individuals had significantly higher MDSC levels than healthy controls which was positively correlated with the viral load and negatively correlated with CD4 + T cell count. Qin et al (2013) found a significant increase of MDSCs in HIV-1-seropositive patients in comparison with healthy controls even in the presence of efficient anti-retroviral therapy. A high MDSC frequency again correlated with HIV-1 disease markers and CD4 + T cell loss.…”

Section: Mdscs As a Target For Diseases Of Ageingmentioning

confidence: 86%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.

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Section: Mdscs As a Target For Diseases Of Ageingmentioning

confidence: 86%

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Bueno

Sant’Anna

Lord

2014

AGE

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“…52 Cell-to-cell contact appears to be essential for these mechanisms. 53 However, the mechanisms by which MDSCs promote cancer cell EMT, proliferation, invasion and metastasis are unclear. Here, we found that the EMT of NPC cells induced by T-MDSCs depended on the existence of cell-to-cell contact between NPC cells and T-MDSCs, which upregulated the expression of COX-2 in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

OuYang

et al. 2015

OncoImmunology

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Keywords: COX-2, myeloid-derived suppressor cells, nasopharyngeal carcinomaAbbreviations: ARG-1, arginase 1; COX-2, cyclooxygenase-2; DFS, disease-free survival; EMT, epithelial-mesenchymal transition; GM-CSF, granulocyte-monocyte-colony stimulating factor; iNOS, inducible nitric oxide synthase; LNMMA, L-NG-monomethylarginine; MDSCs, myeloid-derived suppressor cells; NAC, N-acetylcysteine; NOHA, N-hydroxy-nor-L-arginine; NOX2, NADPH oxidase; NPC, nasopharyngeal carcinoma; ROS, reactive oxygen species; siRNA, small interfering RNA; TCF4, T-cell factor 4; TGF, transforming growth factor b; T-MDSCs, tumor-induced MDSCs; VEGF, vascular endothelial growth factorThe expansion of myeloid-derived suppressor cells (MDSCs) is a common feature of cancer, but its biological roles and molecular mechanism remain unclear. Here, we investigated a molecular link between MDSC expansion and tumor cell metastasis in nasopharyngeal carcinoma (NPC). We demonstrated that MDSCs expanded and were positively correlated with the elevated tumor COX-2 expression and serum IL-6 levels in NPC patients. Importantly, COX-2 and MDSCs were poor predictors of patient disease-free survival (DFS). Knocking down tumor COX-2 expression hampered functional TW03-mediated-MDSC cell (T-MDSC) induction with IL-6 blocking. We identified that T-MDSCs promoted NPC cell migration and invasion by triggering the epithelial-mesenchymal transition (EMT) on cell-to-cell contact, and TMDSCs enhanced tumor experimental lung metastasis in vivo. Interestingly, the contact between T-MDSCs and NPC cells enhanced tumor COX-2 expression, which subsequently activated the b-catenin/TCF4 pathway, resulting in EMT of the cancer cells. Blocking transforming growth factor b (TGFb) or inducible nitric oxide synthase (iNOS) significantly abolished the T-MDSC-induced upregulation of COX-2 and EMT scores in NPC cells, whereas the administration of TGFb or L-arginine supplements upregulated COX-2 expression and EMT scores in NPC cells. These findings reveal that COX-2 is a key factor mediating the interaction between MDSCs and tumor cells, suggesting that the inhibition of COX-2 or MDSCs has the potential to suppress NPC metastasis.

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“…Accumulating evidence has demonstrated that MDSCs were closely associated with disease progression in malignancy and some inflammation-mediated pathological conditions (7,16). Although recent studies report MDSC expansion in viral infections (17)(18)(19)(20)(21)(22), phenotypic and functional features of MDSCs are still poorly defined in patients with CHB. The aim of this study was to determine whether MDSCs are involved in the impaired immune response leading to chronic HBV infection.…”

Section: Hla-drmentioning

confidence: 99%

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

Huang

Zhang

Yan

et al. 2014

The Journal of Immunology

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Although myeloid-derived suppressor cells (MDSCs) are well known for their immunosuppressive function in several pathological conditions, the role of MDSCs in hepatitis B virus infection remains obscure. In this study, we investigated the frequency and function of MDSCs in the peripheral blood and liver of 91 chronic hepatitis B (CHB) patients. A higher percentage of MDSCs, defined as CD14+HLA-DR−/low, was detected in peripheral blood of CHB patients than that of the healthy controls. Moreover, high expression of programmed death 1 (PD-1) and secretion of IL-10 in this population were determined. The frequency of MDSCs was positively correlated with serum viral load, but it was negatively correlated with liver inflammatory injury. These cells were also abundant in liver tissue of CHB patients and were related to necroinflammatory activity. Furthermore, we found that these cells could suppress hepatitis B virus–specific CD8+ T cell response, including reduced proliferation and IFN-γ production, and inhibit degranulation of CD8+ T cells, including reduced production of granzyme B and perforin. Importantly, PD-1–induced IL-10 production by MDSCs was responsible for the suppressive activity. To our knowledge, for the first time our study proved that CD14+HLA-DR–/lowPD-1+ MDSCs in CHB patients contribute to an inadequate immune response against the virus and lead to chronic infection, which represents a potential target for therapeutic intervention.

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Expansion of Monocytic Myeloid-Derived Suppressor Cells Dampens T Cell Function in HIV-1-Seropositive Individuals

Cited by 142 publications

References 42 publications

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

COX-2 promotes metastasis in nasopharyngeal carcinoma by mediating interactions between cancer cells and myeloid-derived suppressor cells

Myeloid-Derived Suppressor Cells Regulate Immune Response in Patients with Chronic Hepatitis B Virus Infection through PD-1–Induced IL-10

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