Roles of Tregs in development of hepatocellular carcinoma: a meta-analysis

To assess systematically the association between regulatory T cells (Tregs) and hepatocellular carcinoma (HCC).

We searched Medline, Embase and Wanfang databases for literature on the populations of Tregs in HCC patients and controls, using the pooled OR and 95%CIs for assessment. There were no limitations with respect to publication date or language. The references of qualifying articles were also searched. We excluded studies with unclear data or overlapping studies. Twenty-three studies met our criteria, and the quality of these studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN). The meta-analysis of association between Tregs and HCC was undertaken using the random-effects approach, as described by DerSimonian and Laird. Subgroup analysis was performed when at least three studies were available. Potential publication bias was assessed by visual inspection of the funnel plot, and an asymmetric plot suggested possible publication bias.

Twenty-three studies with a total of 1279 HCC patients and 547 healthy volunteers as controls were enrolled. The frequency of circulating Tregs in HCC patients was 87% higher than in healthy controls (OR = 1.87, 95%CI: 1.49-2.34). The frequency of Tregs in the HCC tumor microenvironment was significantly higher than that in tumor-surrounding tissue and biopsy specimens from healthy livers (OR = 4.04, 95%CI: 2.10-7.79, P = 0.000; OR = 2.869, 95%CI: 2.16-3.82, P = 0.000). However, subgroup analyses based on the different types of tumors or patient characteristics such as tumor size, tumor number or α fetoprotein (AFP) levels in HCC patients, showed that populations of Tregs as a whole were not significantly changed between groups (P > 0.05 for all).

There is an obvious association between Tregs and pathogenesis of HCC. Further well-designed clinical studies are warranted to illustrate the potential role of Tregs in HCC.