Prognostic value of tumor-infiltrating lymphocytes in hepatocellular carcinoma A meta-analysis

Background: In patients with hepatocellular carcinoma (HCC), the prognostic role of tumor-infiltrating lymphocytes (TILs) for survival is still controversial. A meta-analysis was performed to investigate the prognostic effect of TILs in HCC. Methods: We identify studies from PubMed, Embase, and the Cochrane Library to evaluate the prognostic value of TILs in patients with HCC. A meta-analysis was conducted to estimate overall survival and disease-free survival. The hazard ratio (HR) and 95% confidence interval (CI) were calculated employing fixed-effect or random-effect models depending on the heterogeneity of the included trials. Results: A total of 7905 patients from 46 observational studies were enrolled. For TILs subsets, the density of CD8+, FOXP3+, CD3 +, and Granzyme B+ lymphocytes was significantly associated with improved survival (P<.05). The density of FOXP3+ TILs in intratumor (IT) was the most significant prognostic marker (pooled HR=1.894; 95% CI=1.659-2.164; P<.001). Patients with high infiltration of CD8+ TILs in IT (pooled HR=0.676; 95% CI=0.540-0.845; P=. 001) or in margin of tumor (MT) (pooled HR=0.577; 95% CI=0.437-0.760; P<.001) had better OS. The pooled analysis revealed that high density of Granzyme B+ T-lymphocytes in IT was statistically significant associated with better OS (pooled HR=0.621; 95% CI=0.516-0.748; P<.001) and DFS (pooled HR=0.678; 95% CI=0.563-0.815; P<.001). It was interesting that high density of CD3+ in IT foreboded worse OS (pooled HR=1.008; 95% CI=1.000-1.015; P=. 037), but better DFS (pooled HR=0.596; 95% CI=0.374-0.948; P=. 029). Conclusion: Our findings suggested that some TIL subsets could serve as prognostic biomarkers in HCC. High-quality randomized controlled trials are needed to determine if these TILs could serve as targets for immunotherapy in HCC.