Clinicopathologic and prognostic significance of regulatory T cells in patients with hepatocellular carcinoma: a meta-analysis.

Lejia Sun,Wenjun Liao,Haitao Zhao,Xinting Sang,Haifeng Xu,Shunda Du,Gang Xu,Huayu Yang,Xin Lu,Yilei Mao

doi:10.18632/oncotarget.17340

Abstract

The clinicopathologic and prognostic significance of regulatory T cells (Tregs) in patients with hepatocellular carcinoma (HCC) remains controversial. We performed a meta-analysis to resolve this issue. PubMed, Embase, Cochrane library, and the Web of Science were searched to identify eligible studies performed up to November 2016. A total of 3,854 HCC patients from 27 cohort studies were included. The meta-analysis revealed that high levels of Tregs were associated with poor overall survival (OS; HR = 1.95, P < 0.00001) and disease-free survival (DFS; HR = 1.82, P < 0.00001). However, the prognostic effect varied greatly according to the site of the Tregs. Higher intratumoral and peripheral blood levels of Tregs were associated with shorter OS and DFS, whereas a high peritumoral Tregs level was not associated with decreased OS and DFS. Trial design, therapy and method of detection had no effect on prognosis of Tregs. Moreover, the patients with high Tregs infiltration had multiple tumors, high AFP level, poor differentiation, later TNM stage, and vascular invasion. The present study demonstrates that high levels of intratumoral and peripheral blood Tregs predict multiple tumors, high AFP level, poor differentiation, later TNM stage, and vascular invasion and might be a promising prognostic factor in patients with HCC.

Highlights

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide
Higher intratumoral and peripheral blood levels of regulatory T cells (Tregs) were associated with shorter overall survival (OS) and disease-free survival (DFS), whereas a high peritumoral Tregs level was not associated with decreased OS and DFS
A high Tregs level was associated with poor prognosis in breast cancer [43] but with improved prognosis in colorectal cancer [44]

Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Half of these cases and deaths were estimated to occur in China [1, 2]. The current therapeutic options for HCC are limited to liver surgery and liver transplantation , but tumor recurrence following liver resection and liver transplantation for HCC is common and a major cause of death from this disease [3]. It is necessary to study novel therapeutic strategies. The liver is considered a immune organ and immune escape is one of the mechanisms of hepatocarcinogenesis [4, 5]. The immunological microenvironment is very important for progression of HCC and regulatory T cells (Tregs) are in involved in the immunological microenvironment [6]

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Results

Conclusion