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Annals of Surgical Oncology

, Volume 26, Issue 3, pp 884–893 | Cite as

MiR-21 Participates in the PD-1/PD-L1 Pathway-Mediated Imbalance of Th17/Treg Cells in Patients After Gastric Cancer Resection

  • Xiaoyu Zheng
  • Linlin Dong
  • Kun Wang
  • Huichao Zou
  • Su Zhao
  • Yu Wang
  • Guonian WangEmail author
Translational Research and Biomarkers
  • 139 Downloads

Abstract

Background

The programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway has been shown to be involved in trauma-induced immunosuppression and to influence CD4+ T cell differentiation. MicroRNA (miR)-21 is a critical player in immune responses. However, it remains largely unknown whether miR-21 is regulated by PD-1 and influences CD4+ T-cell lineage choice after gastric cancer resection.

Methods

In the present study, we analyzed the percentages of T-helper (Th)-17/regulatory T (Treg) cells and PD-1/PD-L1 expression on peripheral blood mononuclear cells (PBMCs) during the perioperative period. We also detected the secretion of interleukin (IL)-17 and transforming growth factor (TGF)-β1 using enzyme-linked immunosorbent assays (ELISAs). Furthermore, PBMCs isolated from patients were transfected with or without adenovirus-short hairpin-PD-1 (Ad-sh-PD1), pre-miR-21 or adenovirus–green fluorescent protein (Ad-GFP), and the percentages of Th17/Treg cells and related transcription factors were measured.

Results

In patients who underwent gastric cancer resection, the number of Th17 cells decreased, whereas the number of Treg cells increased, accompanied by an increased expression of PD-1/PD-L1. In addition, the expression of RORγt and IL-17 decreased, whereas the expression of Foxp3 and TGF-β1 increased. In vitro, silencing PD-1 via Ad-sh-PD1 promoted the expression of miR-21 and increased the percentage of Th17 cells, but decreased the percentage of Treg cells. The overexpression of miR-21 increased the percentage of Th17 cells but decreased the percentage of Treg cells.

Conclusions

Our study demonstrated that gastric cancer resection altered the balance of Th17/Treg cells and increased PD-1/PD-L1 expression. In the in vitro experiments, the transfection of Ad-sh-PD1 ameliorated Th17/Treg cell imbalance partially by increasing the expression of miR-21.

Notes

Acknowledgment

This study was funded by the foundation of the National Natural Science Foundation of China (Grant No. 81571885), the Nn10 program of the Harbin Medical University Cancer Hospital and the Foundation of Heilongjiang Academy of Medical Sciences (Grant No. 201808).

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Copyright information

© Society of Surgical Oncology 2018

Authors and Affiliations

  • Xiaoyu Zheng
    • 1
  • Linlin Dong
    • 1
  • Kun Wang
    • 1
  • Huichao Zou
    • 1
  • Su Zhao
    • 3
  • Yu Wang
    • 1
  • Guonian Wang
    • 1
    • 2
    Email author
  1. 1.Department of AnaesthesiologyHarbin Medical University Cancer HospitalHarbinChina
  2. 2.Pain Research Institute of Heilongjiang Academy of Medical SciencesHarbinChina
  3. 3.Department of Thoracic SurgeryHarbin Medical University Cancer HospitalHarbinChina

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