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

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.