Abstract
Background: CD4+CD25+ forkhead box P3 (FOXP3)+ regulatory T cells (Tregs) accumulate in malignant tumors and negatively regulate antitumor immunity. However, the clinical significance of Tregs in HCC remains unclear. To determine the prognostic value of Tregs, we conducted a retrospective study on 264 patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) who underwent transcatheter arterial chemoembolization (TACE).
Methods: We measured the proportion of peripheral blood Tregs in 105 healthy donors and 264 HCC patients (stage B) prior to and following TACE between 2005 and 2007. All HCC patients were followed up until December 2012. The correlations between the proportion of Tregs and clinicopathologic factors were analyzed, and long-term survival rate after TACE according to the percentage of Tregs was assessed by univariate and multivariate analyses.
Results: The 1-, 2-, 3-, 4- and 5-year cumulative survival rates were 62.1%, 32.6%, 16.5%, 10.4% and 6.9%, respectively, and the median survival time was 19.0 months. The cumulative survival rate was significantly lower in patients with higher levels of peripheral blood Treg cells compared to those with lower Treg levels (p<0.001). Furthermore, we found that both pre- and post-TACE peripheral blood Treg levels showed significant negative association with overall survival time (p<0.001).
Conclusions: Elevated peripheral blood CD4+CD25+FOXP3+Treg levels are an independent predictive factor of poor survival after TACE for HCC (stage B) patients. These results suggest that targeting Tregs may improve patient outcomes, and provide a strong rationale for testing these approaches in future immunotherapy-based clinical trials.
Acknowledgments
Thanks to Dr. Xingding Zhang and Patricia Fox of the University of Texas M.D. Anderson Cancer Center for statistical advice. This work was supported in part by the National Natural Science Foundation of China (No. 81001002, 30973438, 81101754), Tianjin Natural Science Foundation (No. 09JCYBJC10400), Tianjin Health Bureau Foundation (No. 2010KZ7, 2011KZ74) and Tianjin Medical University Science Foundation (No.2011KY14).
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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