The Clinicopathological and Prognostic Implications of FoxP3 Regulatory T Cells in Patients with Colorectal Cancer: A Meta-Analysis.

Forkhead box P3 (FoxP3) is known as the specific marker for regulatory T lymphocytes (Tregs), which are responsible for self-tolerance and disturb the antitumor immunity. However, the prognostic implication of tumor-infiltrating FoxP3 Tregs in patients with colorectal cancer (CRC) still remains controversial. The aim of this present study was to investigate the prognostic role of FoxP3 Tregs in CRC through meta-analysis. PubMed, Embase and Web of Science were searched for relevant articles up to December 12, 2016. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated to explore the prognostic value of FoxP3 Tregs in CRC. Odds ratio (OR) was calculated to investigate the correlation between FoxP3 Tregs and pathological parameters. A total of 18 studies comprising 3,627 patients with CRC were enrolled in our meta-analysis. The combined HR for FoxP3 Tregs on cancer-specific survival was 0.70 (95% CI = 0.62-0.80, < 0.001). High FoxP3 Tregs level was also associated with favorable prognosis on overall survival (HR = 0.76, 95% CI = 0.58-1.01, = 0.058), with -value very close to the statistical threshold. Yet, there was no correlation between FoxP3 Tregs infiltration and disease-free survival (HR = 0.83, 95% CI = 0.63-1.09, = 0.182). Moreover, FoxP3 Tregs infiltration was significantly correlated with pT stage (OR = 0.50, 95% CI = 0.39-0.65, < 0.001), tumor grade (OR = 0.77, 95% CI = 0.61-0.98, = 0.032), lymphatic invasion (OR = 0.25, 95% CI = 0.07-0.89, = 0.033) and vascular invasion (OR = 0.67, 95% CI = 0.52-0.86, = 0.001). The present meta-analysis suggests that high FoxP3 Tregs infiltration is inclined to indicate favorable prognosis and is associated with the pathogenesis of CRC. Immunotherapy targeting Tregs in patients with CRC should be further investigated.