IL-6-stimulated CD11b+CD14+HLA-DR− myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus

Chen, Miao Fen; Kuan, Feng Che; Yen, Tzu Chen; Lu, Ming; Lin, Paul; Chung, Yoon Kyu; Chen, Wen Cheng; Lee, Kuan Der

doi:10.18632/oncotarget.2368

Cited by 137 publications

(133 citation statements)

References 43 publications

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“…S5), calcitriol significantly attenuated the increased IL6 noted in 4-NQO-treated mice, including serum and esophageal lesions. We previously reported that IL6 is associated with MDSC accumulation and invasive tumor progression in vivo (21). Moreover, our data suggested that the inhibition of IL6 was linked to the antitumor effect induced by calcitriol.…”

Section: Effect Of Calcitriol On Tumor Progression In Vivo and Its LIsupporting

confidence: 56%

“…Many of these approaches are likely to be most effective in immunocompetent tumor-bearing individuals who are minimally immunosuppressed. IL6 has been reported linked with the recruitment of MDSCs and tumor progression in esophageal SCC (20,21). MDSCs constitute an immature population of myeloid cells thought to be an important subset of cells that contribute to an immunosuppressive tumor microenvironment (43,44) and are significantly increased in number in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

“…Six-week-old male C57BL/6J mice and IL6 knockout mice on a C57BL/6J background (B6.129S2-Il6tm1Kopf/J; IL6KO) were used for the 4-NQO-induced esophageal tumor model (21,24). Briefly, the mice were allowed access to drinking water containing 100 mg/mL 4-NQO (tumor-induced group) or solvent only (control group) at all times during the treatment period.…”

Section: Induction Of Esophageal Tumors In Micementioning

confidence: 99%

“…As described previously (21,25), the 4-NQO-induced esophageal tumors were detected using PET. Briefly, the esophageal tumors were detected after the injection of 7.4-9.25 MBq of 2-deoxy-2-[F-18]fluoro-D-glucose via the tail vein 60 minutes before the PET scan, which was performed on an Inveon system (Siemens Medical Solutions Inc.) located in the Molecular Image Center of our hospital.…”

Section: Small-animal Pet Imaging Of Tumormentioning

confidence: 99%

“…In our previous study, IL6 has been demonstrated to link with aggressive tumor behavior and poor prognosis of esophageal SCC (20). Moreover, IL6-induced myeloid-derived suppressor cells (MDSC) recruitment provides a microenvironment conducive to tumor growth and the development of treatment resistance in esophageal SCC (21). Therefore, we also examine the role of calcitriol in cancer prevention and its linkage with IL6 in an animal esophageal tumor model to provide new insights into the development of immune-based therapies.…”

Section: Introductionmentioning

confidence: 99%

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1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The aim of this study was to highlight the role of 1a,25-dihydroxyvitamin D3 (calcitriol) in esophageal squamous cell carcinoma (SCC). The human esophageal SCC cell lines CE81T and TE2 were selected for cellular and animal experiments to investigate the changes in tumor behavior after calcitriol supplementation and the underlying mechanisms. Moreover, we evaluated the relationship between calcitriol supplementation, myeloid-derived suppressor cell (MDSC) recruitment, IL6 levels, and tumor progression by a 4-nitroquinoline 1-oxide (4-NQO)-induced esophageal tumor animal model. In this study, we demonstrated that calcitriol supplementation inhibited aggressive tumor behavior both in vitro and in vivo. The underlying changes included increased cell death, a lower degree of epithelial-mesenchymal transition, and inhibited IL6 signaling. In the 4-NQOinduced esophageal tumor animal model, increased IL6 and MDSC recruitment were linked with invasive esophageal tumors. Supplementation with calcitriol attenuated the level of IL6, the induction of MDSCs, and the incidence of 4-NQO-induced invasive tumors. Moreover, the IL6-induced changes in C57 mice, including augmented MDSC recruitment, increased levels of ROS and p-Stat3 in MDSCs, and higher suppressive function of MDSCs in T-cell proliferation, which were abrogated by calcitriol supplementation. On the basis of our results, we concluded that calcitriol abrogated the IL6-induced aggressive tumor behavior and MDSC recruitment to inhibit esophageal tumor promotion. Therefore, we suggest that supplementation with vitamin D 3 may be a promising strategy for the prevention and treatment of esophageal SCC.

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Section: Effect Of Calcitriol On Tumor Progression In Vivo and Its LIsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Induction Of Esophageal Tumors In Micementioning

confidence: 99%

Section: Small-animal Pet Imaging Of Tumormentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

Chen

Hsieh

et al. 2015

Molecular Cancer Therapeutics

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The role of myeloid‐derived suppressor cells in gastrointestinal cancer

Cui

Lan

2021

Cancer Communications

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Gastrointestinal (GI) cancer encompasses a range of malignancies that originate in the digestive system, which together represent the most common form of cancer diagnosed worldwide. However, despite numerous advances in both diagnostics and treatment, the incidence and mortality rate of GI cancer are on the rise. Myeloid‐derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that increase in number under certain pathological conditions, such as infection and inflammation, and this expansion is of particular relevance to cancer. MDSCs are heavily involved in the regulation of the immune system and act to dampen its response to tumors, favoring the escape of tumor cells from immunosurveillance and increasing both metastasis and recurrence. Several recent studies have supported the use of MDSCs as a prognostic and predictive biomarker in patients with cancer, and potentially as a novel treatment target. In the present review, the mechanisms underlying the immunosuppressive functions of MDSCs are described, and recent researches concerning the involvement of MDSCs in the progression, prognosis, and therapies of GI cancer are reviewed. The aim of this work was to present the development of novel treatments targeting MDSCs in GI cancer in the hope of improving outcomes for patients with this condition.

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MiR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro

et al. 2018

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The monocytic MDSC (M‐MDSC) is one of the major types of MDSCs, which play important roles in suppression of antitumor immunity. However, the mechanisms underlying how M‐MDSCs so heavily accumulate in patients with cancer are still poorly understood. The purpose of this study was to identify miRNAs that regulate the proliferation and differentiation of M‐MDSCs. Microarray analysis was performed to identify differentially expressed miRNAs between tumor‐induced M‐MDSCs (TM‐MDSCs) and their counterparts from tumor‐free mice. The miRNAs and their target genes that regulate the proliferation and differentiation of myeloid cells were predicted by bioinformatics analysis and validated by RT‐qPCR. Luciferase reporter assays were used to analyze the relationships between miRNAs and target genes. Overexpression of candidate miRNAs and target genes in myeloid cells was conducted to verify their functions in cell proliferation, differentiation, and apoptosis. Our data showed that miR‐486 was overexpressed in TM‐MDSCs. Cebpa was predicted to be one of the target genes of miR‐486 that regulates the proliferation of myeloid cells. Expression of Cebpa was inversely correlated with miR‐486 in TM‐MDSCs, and we found that overexpression of miR‐486 suppressed the expression of Cebpa in both 293T cells determined by luciferase reporter assays and in myeloid cells determined by RT‐qPCR. Overexpression of miR‐486 promoted proliferation and suppressed apoptosis in myeloid cells, as opposed to overexpression of Cebpa, which promoted the opposing phenotype. Overexpression of either miR‐486 or Cebpa inhibited differentiation of myeloid cells. This study indicates that miR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro, suggesting that miR‐486 and Cebpa might be involved in the expansion of TM‐MDSCs in tumor‐bearing mice.

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IL-6-stimulated CD11b+CD14+HLA-DR− myeloid-derived suppressor cells, are associated with progression and poor prognosis in squamous cell carcinoma of the esophagus

Cited by 137 publications

References 43 publications

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

1α,25-Dihydroxyvitamin D3 Inhibits Esophageal Squamous Cell Carcinoma Progression by Reducing IL6 Signaling

The role of myeloid‐derived suppressor cells in gastrointestinal cancer

MiR‐486 promotes proliferation and suppresses apoptosis in myeloid cells by targeting Cebpa in vitro

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