Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer

Zhang, Hua; Maric, Irena; DiPrima, Michael; Khan, Javed; Orentas, Rimas J.; Kaplan, Rosandra N.; Mackall, Crystal L.

doi:10.1182/blood-2012-08-449413

Cited by 146 publications

(151 citation statements)

References 54 publications

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“…Many studies have reported that COX-2 expression is usually upregulated in human cancers, including NPC. 34,44,45 COX-2 activity is detected throughout the progression of a premalignant lesion to a metastatic phenotype. Increased expression of COX-2 is associated with angiogenesis, decreased host immunity, enhanced invasion and metastasis in cancers.…”

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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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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“…on their surfaces Gunaydin et al 2015). According to Zhang et al (2013), F-MDSCs might express HLA-DR unlike other human MDSCs. Although it is clear that F-MDSCs with fibrocytic phenotypes show immunosuppressive functions, little is known how F-MDSCs differentiate from common HSCs and suppress T cells.…”

Section: The Subsets Of Mdscsmentioning

confidence: 99%

“…Recently, fibrocytic MDSCs (F-MDSCs) are characterized as a novel MDSC subset in human (Abrams and Waight 2012;Zhang et al 2013;Mazza et al 2014;Zoso et al 2014;Gunaydin et al 2015). F-MDSCs show tumorassociated circulating fibrocyte phenotypes and have T cell-mediated immunosuppressive functions.…”

Section: The Subsets Of Mdscsmentioning

confidence: 99%

“…Treg cells . Previous study showed that tryptophan is an essential amino acid for T cell proliferation and activation, and that IDO depletes tryptophan by degrading it to formylkynurenine, which leads to the inhibition of T cell proliferation during antigen-specific T cell activation in turn (Lee et al 2002, Zhang et al 2013). Besides of this previously known tryptophan depletion mechanism, Zoso et al also showed that 3-hydroxyanthranilic acid, a downstream metabolite for IDO-mediated tryptophan degradation, promotes Treg differentiation by inducing the secretion of immunosuppressive transforming growth factor-b from DCs.…”

Section: The Immunosuppressive Functions Of F-mdscsmentioning

confidence: 99%

“…Zhang et al reported that hematopoietic stem cells (HSC)-derived fibrocytes suppress T cell proliferation through indoleamine oxidase (IDO) production, and that those immunosuppressive fibrocytes are suggested as a novel MDSC subset (Zhang et al 2013). In 2014, Zoso et al named this population as F-MDSCs and showed that the physical interaction between F-MDSCs and T cells induces the production of IDO in F-MDSCs and that F-MDSCsproduced IDO promotes the expansion of immunosuppressive Foxp3 ?…”

Section: The Immunosuppressive Functions Of F-mdscsmentioning

confidence: 99%

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Phenotypic and functional dissection of myeloid-derived suppressor cells

Han

Yang

2016

Appl Biol Chem

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Myeloid-derived suppressor cells (MDSCs) are originated and differentiated population from common hematopoietic progenitor cells. Generally, in the late stage of inflammation, MDSCs differentiation and expansion are promoted to suppress the over-activated immune system so that the immune system can maintain the homeostasis. Recently, it has been revealed that MDSCs accumulate in cancer patients and tumor-bearing experimental animals, and these tumor-derived MDSCs suppress anti-tumor immunity by secreting immunosuppressive cytokines including reactive oxygen species and inducible nitric oxide synthase. This fact prompts scientists to shed light on MDSCs as significant targets for anti-cancer immunotherapy. However, due to morphological, phenotypic, and functional heterogeneities of MDSCs, it is not easy to develop therapeutic strategies targeting MDSCs. In this review, we will summarize recent progress on defined subsets of MDSCs and their strategies to suppress T cellmediated anti-tumor immunity.

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2021

Flow Cytometry of Hematological Malignancies

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Fibrocytes represent a novel MDSC subset circulating in patients with metastatic cancer

Abstract: Key Points Myeloid cells in subjects with cancer contain fibrocytes, a cell subset previously implicated in chronic inflammation. Fibrocytes in cancer patients are immunosuppressive and may contribute to immune escape.

Cited by 146 publications

References 54 publications

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

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

Phenotypic and functional dissection of myeloid-derived suppressor cells

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