Myeloid‐derived suppressor cell heterogeneity in human cancers

Solito, Samantha; Marigo, Ilaria; Pinton, Laura; Damuzzo, Vera; Mandruzzato, Susanna; Bronte, Vincenzo

doi:10.1111/nyas.12469

Cited by 350 publications

(356 citation statements)

References 124 publications

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“…34,35 However, only a few studies have attempted to identify MDSCs in patients with malignant lymphoma. 6 We assessed the percentage of HLA-DR ¡ CD11b C CD33 C MDSCs and CD14 C HLA-DR C monocytes in the peripheral blood of 15 patients with NHL ( Table 1) and 12 healthy controls and found that HLA-DR ¡ CD11b C CD33 C MDSCs, but not CD14 C HLA-DR C monocytes were significantly increased in NHL patients compared to healthy controls ( Fig.…”

Section: Inverse Correlation In the Number Of Mdscs And Nk Cells In Lmentioning

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: Inverse Correlation In the Number Of Mdscs And Nk Cells In Lmentioning

confidence: 99%

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

et al. 2015

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“…Moreover, it has been suggested that several human MDSC phenotypes can be endowed with suppressive activity. 91 Thus, further studies are required to better define the roles and functions of different MDSC phenotypes in TC.…”

Section: Mdscs: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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“…14,15 The MDSC phenotype varies by differentiation status and function in response to the environmental conditions of different cancers and generally has been termed as the HLA-DR ¡ CD33 C CD11b C cell population, including PMN-and MO-MDSCs, in many human cancers. [16][17][18][19] In humans, these tumor-associated MDSCs have drawn attention due to their role in tumor progression. MDSCs enhance tumor growth by negatively regulating immune responses and facilitating tumor metastasis and angiogenesis.…”

Section: Cox-2 Promotes Metastasis In Nasopharyngeal Carcinoma By Medmentioning

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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Myeloid‐derived suppressor cell heterogeneity in human cancers

Cited by 350 publications

References 124 publications

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

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

The immune network in thyroid cancer

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

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