The Prognostic Value of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Abstract

Abstract Previous clinical studies have found that the levels of tumor-infiltrating lymphocytes (TILs) significantly correlated with prognosis in hepatocellular carcinoma (HCC). However, these conclusions and data remain controversial. We performed a systematic review and meta-analysis to assess the prognostic value and clinical utilization of TILs in patients with HCC. A total of 23 relevant studies of 3173 patients were included into our meta-analysis. The results demonstrated that high levels of CD8 + and CD3 + TILs had a better prognostic value on overall survival (OS), with HRs of 0.71 (P = 0.04) and 0.63 (P = 0.03), respectively, compared to low levels, as did high levels of CD8 + , CD3 + and CD4 + TILs on disease/recurrence-free survival (DFS/RFS), with HRs of 0.66 (P = 0.01), 0.60 (P = 0.01) and 0.79 (P = 0.04), respectively. In contrast, high levels of FoxP3 + TILs had a worse prognostic value on OS and DFS/RFS, with HRs of 2.06 (P < 0.00001) and 1.77 (P < 0.00001), respectively. The FoxP3+/CD4+ and FoxP3+/CD8+ ratios negatively correlated with OS and DFS/RFS. These findings suggest that TILs may serve as a prognostic biomarker in HCC. However, further research should be performed to clarify the clinical value of TILs in HCC.