Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct 14;18(38):5454-61.
doi: 10.3748/wjg.v18.i38.5454.

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

Zhi-Jun Jiao  1 , Jing-Jing Gao, Sheng-Hao Hua, De-Yu Chen, Wen-Hong Wang, Hui Wang, Xu-Hui Wang, Hua-Xi Xu
Affiliations

Correlation between circulating myeloid-derived suppressor cells and Th17 cells in esophageal cancer

Zhi-Jun Jiao et al. World J Gastroenterol. .

Abstract

Aim: To perform a comprehensive investigation into the potential correlation between circulating myeloid-derived suppressor cells (MDSCs) and Th17 cells in esophageal cancer (ECA).

Methods: A total of 31 patients newly diagnosed with ECA and 26 healthy subjects were included in the current study. The frequencies of MDSCs and Th17 cells in peripheral blood were determined by flow cytometry. The mRNA expression of cytokines, arginase 1 (Arg1) and inducible NO synthase (iNOS) in peripheral blood mononuclear cells (PBMCs) and plasma Arg1 were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Results: There was an increased prevalence of MDSCs in the peripheral blood from ECA patients (15.21% ± 2.25%) when compared with healthy control (HC) (1.10% ± 0.12%, P < 0.0001). The plasma levels of Arg1 in ECA patients were significantly higher than those in HC (28.28 ± 4.10 ng/mL vs 9.57 ± 1.51 ng/mL, P = 0.0003). iNOS mRNA levels in the peripheral blood of ECA patients also showed a threefold increase compared with HC (P = 0.0162). The frequencies of Th17 cells (CD4⁺IL-17A⁺) were significantly elevated in ECA patients versus HC (3.50% ± 0.33% vs 1.82% ± 0.19%, P = 0.0001). Increased mRNA expression of IL-17 and ROR-γt was also observed in ECA patients compared with HC (P = 0.0041 and P = 0.0004, respectively), while the mRNA expression of IL-6 and tumor necrosis factor-α (TNF-α) showed significant decreases (P = 0.0049 and P < 0.0001, respectively). No obvious correlations were found between the frequencies of MDSCs and Th17 cells in the peripheral blood from ECA patients(r = -0.1725, P = 0.3534). Arg1 mRNA levels were positively correlated with levels of IL-6 (r = 0.6404, P = 0.0031) and TNF-α (r = 0.7646, P = 0.0001). Similarly, iNOS mRNA levels were also positively correlated with levels of IL-6 (r = 0.6782, P = 0.0007) and TNF-α (r = 0.7633, P < 0.0001).

Conclusion: This study reveals the relationship between circulating MDSCs and Th17 cells, which may lead to new immunotherapy approaches for ECA based on the associated metabolites and cytokines.

Keywords: Arginase I; Esophageal cancer; Inducible NO synthase; Myeloid-derived suppressor cells; Peripheral blood mononuclear cells; Th17 cells.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Elevated levels of myeloid-derived suppressor cells and their products, arginase 1 and inducible NO synthase, in esophageal cancer compared with healthy controls. A: Flow cytometric analysis of MDSCs in the peripheral blood from ECA patients and healthy control (HC); B: Plasma arginase 1 (Arg1) level was determined by ELISA; C: The mRNA level of iNOS in the peripheral blood from ECA patients and HC were assessed by real-time PCR; D: Representative flow diagrams of a healthy volunteer with marked elevation of circulating MDSCs; E: Representative flow diagrams of an ECA patient with marked elevation of circulating MDSCs are shown. Data were analyzed by the Student’s t-test. aP < 0.05, bP < 0.01 vs HC group. ECA: Esophageal cancer; MDSCs: Myeloid-derived suppressor cells; ELISA: Enzyme linked immunosorbent assay; iNOS: Inducible NO synthase; PCR: Polymerase chain reaction; FITC: Fluorescein isothiocyanate; FSC: Forward scatter; HLA-DR-PE: HLA-DR-phycoerythrin; APC: Allophycocyanin.
Figure 2
Figure 2
Levels of Th17 cells and Th17-related cytokines and transcriptional factor in the peripheral blood of esophageal cancer compared with healthy controls. A: Flow cytometric analysis of Th17 cells in the peripheral blood from ECA patients and healthy control (HC); B: The mRNA levels of IL-17 was determined by real-time PCR; C: The mRNA levels of ROR-γt was determined by real-time PCR; D: The mRNA levels of IL-6 was determined by real-time PCR; E: The mRNA levels of TNF-α was determined by real-time PCR; F: Representative flow diagrams of a healthy volunteer with marked elevation of circulating Th17 cells; G: Representative flow diagrams of an ECA patient with marked elevation of circulating Th17 cells are shown. Data were analyzed by the Student’s t-test. aP < 0.05, bP < 0.01 vs HC group. ECA: Esophageal cancer; TNF-α: Tumor necrosis factor-α; IL: Interleukin; PCR: Polymerase chain reaction; FITC: Fluorescein isothiocyanate; FSC: Forward scatter; SSC: Side scatter.
Figure 3
Figure 3
Correlation between the frequencies of myeloid-derived suppressor cells and Th17 cells in the peripheral blood of esophageal cancer patients. Data were analyzed by the Spearman test. MDSCs: Myeloid-derived suppressor cells.
Figure 4
Figure 4
Correlations between the mRNA level of arginase 1 or inducible NO synthase and Th17-related molecules (interleukin-17, ROR-γt, interleukin-6 and tumor necrosis factor-α) in the peripheral blood of esophageal cancer patients. Data were analyzed by the Spearman test. aP < 0.05, bP < 0.01 vs β-actin. TNF-α: Tumor necrosis factor-α; IL: Interleukin; iNOS: Inducible NO synthase; Arg1: Arginase 1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9:162–174. - PMC - PubMed
    1. Raychaudhuri B, Rayman P, Ireland J, Ko J, Rini B, Borden EC, Garcia J, Vogelbaum MA, Finke J. Myeloid-derived suppressor cell accumulation and function in patients with newly diagnosed glioblastoma. Neuro Oncol. 2011;13:591–599. - PMC - PubMed
    1. Brandau S, Trellakis S, Bruderek K, Schmaltz D, Steller G, Elian M, Suttmann H, Schenck M, Welling J, Zabel P, et al. Myeloid-derived suppressor cells in the peripheral blood of cancer patients contain a subset of immature neutrophils with impaired migratory properties. J Leukoc Biol. 2011;89:311–317. - PubMed
    1. Almand B, Clark JI, Nikitina E, van Beynen J, English NR, Knight SC, Carbone DP, Gabrilovich DI. Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001;166:678–689. - PubMed
    1. Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, Zanon A, Rossi CR, Nitti D, Bronte V, et al. IL4Ralpha+ myeloid-derived suppressor cell expansion in cancer patients. J Immunol. 2009;182:6562–6568. - PubMed

Publication types