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Increased CD4+CD69+CD25- T cells in patients with hepatocellular carcinoma are associated with tumor progression

Authors


Dr Sanyuan Hu, Department of General Surgery, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan 250012 Shandong, China. Email: husanyuan1962@hotmail.com; or Xun Qu, Institute of Basic Medical Sciences, Qilu Hospital, Shandong University, 107#, Wenhua Xi Road, Jinan 250012 Shandong, China. Email: quxun@sdu.edu.cn

Abstract

Background and Aim:  A new subset of Treg cells, CD4+CD69+CD25- T cells, has been identified in mice. Herein, we aimed to identify this subset of T cells and to evaluate its function in patients with hepatocellular carcinoma (HCC).

Methods:  We detected CD4+CD69+CD25- T cells and its expression of CCR6 and transforming growth factor-β1 (TGF-β1) in peripheral blood of 91 HCC patients, 38 chronic hepatitis patients and 34 healthy donors by flow cytometry. CD4+CD69+CD25- T cells in HCC tissues were also analyzed.

Results:  CD4+CD69+CD25- T cells were significantly increased in peripheral blood of HCC patients compared with healthy persons and chronic hepatitis patients (8.74% ± 0.42% vs 4.55% ± 0.33% and 5.15% ± 0.36%, P < 0.0001). The percentage of peripheral CD4+CD69+CD25- T cells was significantly higher in HCC patients with Tumor Node Metastasis (TNM) stage III plus IV (P < 0.05). Patients with large tumor size and tumor vascular invasion were inclined to obtain high percentage of CD4+CD69+CD25- T cells (P < 0.05). The frequency of membrane-bound TGF-β1 positive cells in CD4+CD69+CD25- T cells from HCC patients was higher than that from the other two groups (P < 0.0001). A considerable proportion of CD4+CD69+CD25- T cells were present in HCC tissues, which has significant correlation with tumor size and TNM stage. Few CD4+CD69+CD25- T cells express CCR6 both in peripheral blood and tumor tissues from HCC patients.

Conclusions:  Increased CD4+CD69+CD25- T cells in HCC patients are significantly correlated with tumor size, vascular invasion and TNM stage. Thus, increased CD4+CD69+CD25- T cells exert a critical role in HCC progression and might be a clinically aggressive phenotype of HCC.

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