Response to Comment on “Myeloid-Derived Suppressor Cells Suppress Antitumor Immune Responses through IDO Expression and Correlate with Lymph Node Metastasis in Patients with Breast Cancer”

Yu, Jinpu; Wang, Yue; Fang, Yan; Li, Hui; Ren, Xiubao

doi:10.4049/jimmunol.1390024

Cited by 15 publications

(10 citation statements)

References 7 publications

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“…In correlation with this finding, IDO1 inhibitor increased CD8 + T cells and reduced tumor growth in a transgenic mouse model of cecal gastrointestinal stromal tumors, which was reversed by CD8 + T cell depletion ( 55 ). Furthermore, IDO1 is expressed by MDSCs and regulates the immunosuppressive function of these cells against T cells ( 56 ). Alternatively, the mechanism of anti-T cell immunity of IDO1 can also be attributed to plasmocytoid dendritic cell expression of IDO1 in tumor-draining lymph nodes ( 57 ).…”

Section: An Unusual Role For Ido1 In Suppressing Cecal Ifn-γ-producinmentioning

confidence: 99%

Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease

El–Zaatari

Kao

2017

Front. Immunol.

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The host immune response to gastrointestinal (GI) infections, hypersensitivity reactions, or GI cancers comprises numerous pathways that elicit responses on different host cells. Some of these include (1) the stimulation of mast cells via their IgE receptor, (2) the production of antibodies leading to antibody-mediated cytotoxic T/natural killer cell killing, (3) the activation of the complement pathway, and (4) the activation of the adaptive immune response via antigen-presenting cell, T cell, and B cell interactions. Within the plethora of these different responses, several host immune cells represent major key players such as those of myeloid lineage (including neutrophils, macrophages, myeloid-derived suppressor cells) or lymphoid lineage (including T and B cells). In this review, we focus on newly identified metabolites and metabolite receptors that are expressed by either myeloid or lymphoid lineages. Irrespective of their source, these metabolites can in certain instances elicit responses on a wide range of cell types. The myeloid-expressed metabolic enzymes and receptors which we will discuss in this review include arginase 2 (Arg2), indoleamine-2,3-dioxygenase 1 (IDO1), hydroxycarboxylic acid receptor 2 (Hcar2; also called GPR109A), and immunoresponsive gene 1 (Irg1). We will also review the role of the lymphoid-expressed metabolite receptor that binds to the sphingosine-1-phosphate (S1P) sphingolipid. Moreover, we will describe the synthesis and metabolism of retinoic acid, and its effect on T cell activation. The review will then discuss the function of these metabolites in the context of GI disease. The review provides evidence that metabolic pathways operate in a disease- and context-dependent manner—either independently or concomitantly—in the GI tract. Therefore, an integrated approach and combinatorial analyses are necessary to devise new therapeutic strategies that can synergistically improve prognoses.

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Section: An Unusual Role For Ido1 In Suppressing Cecal Ifn-γ-producinmentioning

confidence: 99%

Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease

El–Zaatari

Kao

2017

Front. Immunol.

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“…In addition, M-MDSC were shown to recruit regulatory T cells (Treg) in the tumor (22), and promote de novo induction of FoxP3 + Treg (23), thus spreading the immune suppression further. Different mechanisms were described to contribute their capacity to induce Treg, including the involvement of CD80, TGF-β (24), PD1L (25), IDO-1 (26), ILT-3 (27), and ILT-4 (7, 28). However, it has been shown that these molecules are also involved in the induction of non-conventional Treg subsets, such as suppressor CD8 + and type 1 regulatory T (Tr-1) cells (29, 30).…”

Section: Introductionmentioning

confidence: 99%

Prostaglanin-E2 Potentiates the Suppressive Functions of Human Mononuclear Myeloid-Derived Suppressor Cells and Increases Their Capacity to Expand IL-10-Producing Regulatory T Cell Subsets

et al. 2019

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Myeloid-derived suppressor cells (MDSC) emerged as major factors driving the tumor progression due to numerous immunosuppressive mechanisms they possess. Prostaglandin (PG)E2 is shown critical for the induction of MDSC and their suppressive functions in vivo, but it is poorly understood how it affects the capacity of MDSC to induce different subsets of regulatory T cells (Treg). By using a novel protocol for the generation of mononuclear (M)-MDSC, we showed that PGE2 potentiates the GM-CSF/IL-6-dependent induction of CD33+CD11b+HLA-DR−CD14+ M-MDSC in vitro. PGE2 diminished the capacity of GM-CSF/IL-6 M-MDSC to produce proinflammatory cytokines upon activation and augmented their capacity to produce IL-27, IL-33, and TGF-β. These results correlated with an increased potential of GM-CSF/IL-6/PGE2 M-MDSC to suppress T cell proliferation, expand alloreactive Th2 cells, and reduce the development of alloreactive Th17 and cytotoxic T cells. Interestingly, GM-CSF/IL-6/PGE2 M-MDSC displayed a lower capacity to induce TGF-β-producing FoxP3+ regulatory Treg compared to GM-CSF/IL-6 M-MDSC, as a consequence of reduced IDO-1 expression. In contrast, GM-CSF/IL-6/PGE2 M-MDSC potentiated IL-10 production by CD8+T, Th2, and particularly CD4+FoxP3− type 1 Treg, the latter of which depended on ILT3 and ILT4 expression. Cumulatively, PGE2 potentiated the suppressive phenotype and functions of GM-CSF/IL-6-induced M-MDSC and changed the mechanisms involved in Treg induction, which could be important for investigating new therapeutic strategies focused on MDSC-related effects in tumors and autoimmune diseases.

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“…Myeloid-derived suppressor cells (MDSCs) accumulate in the tumor microenvironment, leading to immune escape of tumor cells. 78 There are differences in the expression of IL-8 in cancer patients, which can be used as the clinical stage, prognosis and disease monitoring indicators of esophageal cancer. Tang et al 79 reported that IL-8 levels in early and advanced esophageal cancer tissues were significantly higher than those in normal esophageal tissues ( P <0.05).…”

Section: Discussionmentioning

confidence: 99%

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips

Tong

Wang

et al. 2018

OTT

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BackgroundThe diagnosis rate of early stage esophageal squamous cell carcinoma (ESCC) is low due to the lack of specific tumor markers. Seeking for these markers is beneficial to improve the early diagnosis rate and the prognosis of patients. This study profiles the differentially expressed proteins of early stage ESCC patients via the AAH-BLG-507 protein chip, which further consolidates the clinical evidence of ESCC diagnosis.Materials and methodsIn this study, 20 serum samples were collected from Taihe Hospital between August 2016 and June 2017. Ten of them carried ESCC, while the rest were healthy controls. To profile the proteins’ expression level, the AAH-BLG-507 protein chip was used, and both highly expressed and lowly expressed proteins were fished out. Meanwhile, their biological roles were examined by using Gene Ontology (GO) database and String database, and they were further verified by ELISA.ResultsResults showed that the expression levels of AXL, ARTN, Ang2, BDNF, BMP7, cripto-1, CCL28, E-selectin, IL-6, IL-8 and SHH in the serum of early ESCC were significantly upregulated (P<0.05), particularly IL-6 and IL-8. The expression levels of TSP1 and MMP-8 were markedly downregulated (P<0.05). Analysis showed that these proteins were mainly involved in angiogenesis, signal transduction, cell proliferation and migration, indicating the close relationship with the development of ESCC.ConclusionIt suggested that IL-6 and IL-8 proteins could be considered as the markers for ESCC diagnosis.

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Response to Comment on “Myeloid-Derived Suppressor Cells Suppress Antitumor Immune Responses through IDO Expression and Correlate with Lymph Node Metastasis in Patients with Breast Cancer”

Cited by 15 publications

References 7 publications

Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease

Role of Dietary Metabolites in Regulating the Host Immune Response in Gastrointestinal Disease

Prostaglanin-E2 Potentiates the Suppressive Functions of Human Mononuclear Myeloid-Derived Suppressor Cells and Increases Their Capacity to Expand IL-10-Producing Regulatory T Cell Subsets

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips

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