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


CONCLUSIONS
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.
Key Laboratory of Medical Immunology, Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212013, Jiangsu Province, China. jiaozhijun@yahoo.com.cn
Zhi-Jun
ZJ
Jiao
Jing-Jing
JJ
Gao
Sheng-Hao
SH
Hua
De-Yu
DY
Chen
Wen-Hong
WH
Wang
Hui
H
Wang
Xu-Hui
XH
Wang
Hua-Xi
HX
Xu
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000097:blood*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000378:metabolism*; D023461:Myeloid Progenitor Cells / Q000378:metabolism; D016133:Polymerase Chain Reaction; D058504:Th17 Cells / Q000378:metabolism*
D014408:Biomarkers, Tumor; D016207:Cytokines