Improved performance of Hangzhou criteria for liver transplantation of hepatocellular carcinoma: the role of liver resident FoxP3+ regulatory T cells.

Tumor-infiltrating lymphocytes (TILs) represent the host immune response to a tumor. In this study, we investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in liver transplant candidates with hepatocellular carcinoma (HCC) and established an improved prognostic model for predicting clinical outcome. CD3+, CD4+, CD8+, and FoxP3+ TILs were assessed by immunohistochemistry in tumor tissue from 153 patients who had undergone liver transplantation for HCC. Prognostic effects of these TIL subsets and other clinicopathologic factors were evaluated by Kaplan-Meier and Cox regression analysis. The area under the curve (AUC) and net reclassification improvement (NRI) were calculated to determine if the new model improved risk prediction. We found that the prevalence of intra-tumoral FoxP3+ Tregs among CD4+ TILs, but not the density of intra-tumoral FoxP3+ Tregs, was an independent predictor for disease-free (DFS) and overall survival (OS) (P<0.05). A Cox model combining the prevalence of intra-tumoral FoxP3+ Tregs with Hangzhou criteria was highly predictive of tumor recurrence and death. The AUCs of the Cox model for recurrence (0.733; 95% CI, 0.656-0.802) and survival (0.765; 95% CI, 0.690-0.830) were significantly increased when compared with those of Hangzhou criteria (P<0.001). Net reclassification improvement showed that predictability of the Cox models for both recurrence and survival was superior to Hangzhou criteria (P<0.05). Our results collectively showed that the prevalence of intra-tumoral FoxP3+ Tregs is a promising prognostic predictor for HCC patients after OLT. Inclusion of FoxP3+ Tregs into Hangzhou criteria could improveme risk prediction. IJCEP