2995 - Dysregulation of helper T lymphocytes in esophageal squamous cell carcinoma (ESCC) patients is highly associated with aberrant production of miR-21

Background

Dysregulation of helper T (Th) cell subsets has been contributed to the initiation and propagation of esophageal squamous cell carcinoma (ESCC). Different microRNAs (miRNAs) have been reported to control the development and functions of tumor-associated immune cells in ESCC. Here, we aimed to assess the IL-10, TGF-β, IFN-γ and IL-17a producing CD3⁺CD8^- T cells in association whit miR-21, miR-29b, miR-106a and miR-155 expression in ESCC patients.

Methods

A total of 34 ESCC patients including 12 newly diagnosed (ND) and 22 under-treatment (UT) cases and 34 age-matched healthy donors were enrolled. Flowcytometric characterization of stimulated T cells was performed by staining cells with fluorescent conjugated specific anti human CD3 and CD8 cell surface markers as well as IL-17a, IFN-γ, IL-10 and TGF-β intracytoplasmic cytokines. Circulating RNA was extracted from the plasma and qRT-PCR was used to evaluate the expression of miR-21 and miR-29b. TGF-β plasma levels were also assessed by ELISA.

Results

The frequency of Th cells was significantly reduced in EC Patients. A significant increase in Tregs as well as Th17 cells population in both patient subgroups was observed. ND patients showed elevated level of Th1 cells and IL-10. However, the expression of IFN-γ was significantly decreased in Th cells. We also detected higher level of miR-21 in the ESCC patients which was significantly correlated with different subsets of Th cell.

Conclusions

Our findings revealed that immune response related Th cells is highly impaired in ESCC patients and association between miR-21 and Th subsets could be correlated with the impairment of anti-tumor immunity and consequently ESCC pathogenesis which might be potentially used as an important target for immunotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Golestan University of Medical Sciences; Semnan University of Medical Sciences.

Disclosure

All authors have declared no conflicts of interest.